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<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="Yes"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19 | The Protein Journal </title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19"/> <meta name="twitter:description" content="The Protein Journal - The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory syndrome..."/> <meta name="twitter:image" content="https://static-content.springer.com/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig1_HTML.png"/> <meta name="journal_id" content="10930"/> <meta name="dc.title" content="The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19"/> <meta name="dc.source" content="The Protein Journal 2020 39:3"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2020-05-23"/> <meta name="dc.type" content="ReviewPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2020 The Author(s)"/> <meta name="dc.rights" content="2020 The Author(s)"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with new cases and deaths growing at an exponential rate. In order to provide a better understanding of SARS CoV-2, this article will review the proteins found in the SARS CoV-2 that caused this global pandemic."/> <meta name="prism.issn" content="1875-8355"/> <meta name="prism.publicationName" content="The Protein Journal"/> <meta name="prism.publicationDate" content="2020-05-23"/> <meta name="prism.volume" content="39"/> <meta name="prism.number" content="3"/> <meta name="prism.section" content="ReviewPaper"/> <meta name="prism.startingPage" content="198"/> <meta name="prism.endingPage" content="216"/> <meta name="prism.copyright" content="2020 The Author(s)"/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s10930-020-09901-4"/> <meta name="prism.doi" content="doi:10.1007/s10930-020-09901-4"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s10930-020-09901-4.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s10930-020-09901-4"/> <meta name="citation_journal_title" content="The Protein Journal"/> <meta name="citation_journal_abbrev" content="Protein J"/> <meta name="citation_publisher" content="Springer US"/> <meta name="citation_issn" content="1875-8355"/> <meta name="citation_title" content="The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19"/> <meta name="citation_volume" content="39"/> <meta name="citation_issue" content="3"/> <meta name="citation_publication_date" content="2020/06"/> <meta name="citation_online_date" content="2020/05/23"/> <meta name="citation_firstpage" content="198"/> <meta name="citation_lastpage" content="216"/> <meta name="citation_article_type" content="Article"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s10930-020-09901-4"/> <meta name="DOI" content="10.1007/s10930-020-09901-4"/> <meta name="size" content="420127"/> <meta name="citation_doi" content="10.1007/s10930-020-09901-4"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s10930-020-09901-4&api_key="/> <meta name="description" content="The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory s"/> <meta name="dc.creator" content="Yoshimoto, Francis K."/> <meta name="dc.subject" content="Bioorganic Chemistry"/> <meta name="dc.subject" content="Biochemistry, general"/> <meta name="dc.subject" content="Organic Chemistry"/> <meta name="dc.subject" content="Animal Anatomy / Morphology / Histology"/> <meta name="citation_reference" content="citation_journal_title=J Med Virol; 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Accessed 26 Apr 2020, 6:05 AM"/> <meta name="citation_author" content="Yoshimoto, Francis K."/> <meta name="citation_author_email" content="francis.yoshimoto@utsa.edu"/> <meta name="citation_author_institution" content="Department of Chemistry, The University of Texas at San Antonio (UTSA), San Antonio, USA"/> <meta name="format-detection" content="telephone=no"/> <meta name="citation_cover_date" content="2020/06/01"/> <meta property="og:url" content="https://link.springer.com/article/10.1007/s10930-020-09901-4"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="SpringerLink"/> <meta property="og:title" content="The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19 - The Protein Journal"/> <meta property="og:description" content="The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with new cases and deaths growing at an exponential rate. 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Cause of COVID-19 </div> <div data-test="inCoD" data-track-context="sticky banner"> <div class="c-pdf-container"> <div class="c-pdf-download u-clear-both u-mb-16"> <a href="/content/pdf/10.1007/s10930-020-09901-4.pdf" class="u-button u-button--full-width u-button--primary u-justify-content-space-between c-pdf-download__link" data-article-pdf="true" data-readcube-pdf-url="true" data-test="pdf-link" data-draft-ignore="true" data-track="content_download" data-track-type="article pdf download" data-track-action="download pdf" data-track-label="button" data-track-external download> <span class="c-pdf-download__text">Download PDF</span> <svg aria-hidden="true" focusable="false" width="16" height="16" class="u-icon"><use xlink:href="#icon-eds-i-download-medium"/></svg> </a> </div> </div> </div> </div> </div> <div class="c-article-header"> <header> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Francis_K_-Yoshimoto-Aff1" data-author-popup="auth-Francis_K_-Yoshimoto-Aff1" data-author-search="Yoshimoto, Francis K." data-corresp-id="c1">Francis K. Yoshimoto<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0002-2308-2999"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0002-2308-2999</a></span><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul> <div data-test="article-metrics"> <ul class="app-article-metrics-bar u-list-reset"> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-accesses-medium"></use> </svg>49k <span class="app-article-metrics-bar__label">Accesses</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-altmetric-medium"></use> </svg>32 <span class="app-article-metrics-bar__label">Altmetric</span></p> </li> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon app-article-metrics-bar__icon app-article-metrics-bar__icon--mentions" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-mentions-medium"></use> </svg>1 <span class="app-article-metrics-bar__label">Mention</span></p> </li> <li class="app-article-metrics-bar__item app-article-metrics-bar__item--metrics"> <p class="app-article-metrics-bar__details"><a href="/article/10.1007/s10930-020-09901-4/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Explore all metrics <svg class="u-icon app-article-metrics-bar__arrow-icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-arrow-right-medium"></use> </svg></a></p> </li> </ul> </div> <div class="u-mt-32"> </div> </header> </div> <div data-article-body="true" data-track-component="article body" class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with new cases and deaths growing at an exponential rate. In order to provide a better understanding of SARS CoV-2, this article will review the proteins found in the SARS CoV-2 that caused this global pandemic.</p></div></div></section> <div data-test="cobranding-download"> </div> <section aria-labelledby="inline-recommendations" data-title="Inline Recommendations" class="c-article-recommendations" data-track-component="inline-recommendations"> <h3 class="c-article-recommendations-title" id="inline-recommendations">Similar content being viewed by others</h3> <div class="c-article-recommendations-list"> <div class="c-article-recommendations-list__item"> <article class="c-article-recommendations-card" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="c-article-recommendations-card__img"><img src="https://media.springernature.com/w92h120/springer-static/cover-hires/book/978-3-030-63761-3?as=webp" loading="lazy" alt=""></div> <div class="c-article-recommendations-card__main"> <h3 class="c-article-recommendations-card__heading" itemprop="name headline"> <a class="c-article-recommendations-card__link" itemprop="url" href="https://link.springer.com/10.1007/978-3-030-63761-3_2?fromPaywallRec=false" data-track="select_recommendations_1" data-track-context="inline recommendations" data-track-action="click recommendations inline - 1" data-track-label="10.1007/978-3-030-63761-3_2">Coronaviruses: What Should We Know About the Characteristics of Viruses? 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J Med Virol 92:448–454" href="/article/10.1007/s10930-020-09901-4#ref-CR1" id="ref-link-section-d447967688e309">1</a>] on December 31, 2019 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Gralinski LE, Menachery VD (2020) Return of the Coronavirus: 2019-nCoV. Viruses 12:135" href="/article/10.1007/s10930-020-09901-4#ref-CR2" id="ref-link-section-d447967688e312">2</a>]. Taxonomically, SARS CoV-2 belongs to the realm <i>Riboviria</i>, order <i>Nidovirales</i>, suborder <i>Cornidovirineae</i>, family <i>Coronaviridae</i>, subfamily <i>Orthocoronavirinae</i>, genus <i>Betacoronavirus</i> (lineage B), [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen K-Y (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 9:221–236" href="/article/10.1007/s10930-020-09901-4#ref-CR3" id="ref-link-section-d447967688e334">3</a>] subgenus <i>Sarbecovirus</i>, and the species <i>Severe acute respiratory syndrome-related coronavirus</i>.</p><p>The genome of SARS CoV-2 (NCBI Reference Sequence: NC_045512.2) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, Zhang Z (2020) The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol 92:667–674" href="/article/10.1007/s10930-020-09901-4#ref-CR4" id="ref-link-section-d447967688e346">4</a>] is similar to the genome of the coronavirus that caused the SARS epidemic in 2003 (SARS CoV, NCBI Reference sequence: NC_004718.3) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Khailany RA, Safdar M, Ozaslan M (2020) Genomic characterisation of a novel SARS-CoV-2. Gene Rep 19:100682" href="/article/10.1007/s10930-020-09901-4#ref-CR5" id="ref-link-section-d447967688e349">5</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (2020) The proximal origin of SARS-CoV-2. Nat Med 26:450–455" href="/article/10.1007/s10930-020-09901-4#ref-CR6" id="ref-link-section-d447967688e352">6</a>]. Much of the understanding of the proteins found in SARS CoV-2 are based on the numerous research studies reported on SARS CoV and other related viruses (e.g. MERS CoV) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 7" title="Li Y-H, Hu C-Y, Wu N-P, Yao H-P, Li L-J (2019) Molecular characteristics, functions, and related pathogenicity of MERS-CoV proteins. Engineering 5:940–947" href="/article/10.1007/s10930-020-09901-4#ref-CR7" id="ref-link-section-d447967688e355">7</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, Zhu H, Zhao W, Han Y, Qin C (2019) From SARS to MERS thrusting coronaviruses into the spotlight. Viruses 11:59" href="/article/10.1007/s10930-020-09901-4#ref-CR8" id="ref-link-section-d447967688e358">8</a>]. However, among the recent coronavirus outbreaks in the new millennium (SARS CoV: 2002–2003, MERS CoV: 2012, SARS CoV-2: 2020), SARS CoV-2 mysteriously had the most devastating global impact. Understanding the proteins present in these viruses enable a more rational approach to designing more effective antiviral drugs [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 9" title="Hilgenfeld R (2014) From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J 281:4085–4096" href="/article/10.1007/s10930-020-09901-4#ref-CR9" id="ref-link-section-d447967688e362">9</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 10" title="Calligari P, Bobone S, Ricci G, Bocedi A (2020) Molecular investigation of SARS-CoV-2 proteins and their interactions with antiviral drugs. Viruses 12:445" href="/article/10.1007/s10930-020-09901-4#ref-CR10" id="ref-link-section-d447967688e365">10</a>]. The majority of proteins of SARS CoV have been characterized in detail. The proteins of SARS CoV consist of two large polyproteins: ORF1a and ORF1ab (that proteolytically cleave to form 16 nonstructural proteins), four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N), and eight accessory proteins: ORF3a, ORF3b (NP_828853.1, not present in SARS CoV-2), ORF6, ORF7a, ORF7b, ORF8a, ORF8b, and ORF9b (NP_828859.1, not present in SARS CoV-2). Although accessory proteins have been viewed as dispensable for viral replication in vitro, some have been shown to play an important role in virus-host interactions in vivo [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 11" title="Liu DX, Fung TS, Chong KK-L, Shukla A, Hilgenfeld R (2014) Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 109:97–109" href="/article/10.1007/s10930-020-09901-4#ref-CR11" id="ref-link-section-d447967688e368">11</a>]. Similar to SARS CoV, SARS CoV-2 lacks the hemagglutinin esterase gene, which is found in human coronavirus (hCoV) HKU1, a lineage A betacoronavirus [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen K-Y (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 9:221–236" href="/article/10.1007/s10930-020-09901-4#ref-CR3" id="ref-link-section-d447967688e371">3</a>]. The spike protein, envelope protein, membrane protein, nucleocapsid protein, 3CL protease, papain like protease, RNA polymerase, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 10" title="Calligari P, Bobone S, Ricci G, Bocedi A (2020) Molecular investigation of SARS-CoV-2 proteins and their interactions with antiviral drugs. Viruses 12:445" href="/article/10.1007/s10930-020-09901-4#ref-CR10" id="ref-link-section-d447967688e374">10</a>] and helicase protein have been suggested to be viable antiviral drug targets [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 12" title="Prajapa M, Sarma P, Shekhar N, Avti P, Sinha S, Kaur H, Kumar S, Bhattacharyya A, Kumar H, Bansal S, Medhi B (2020) Drug targets for corona virus: a systematic review. Indian J Pharmacol 52:56–65" href="/article/10.1007/s10930-020-09901-4#ref-CR12" id="ref-link-section-d447967688e377">12</a>]. SARS CoV-2 is an RNA virus and its RNA genome is 30 kb in length. SARS CoV-2 is thought to have originated from its closest relative, BatCov RaTG13 (GenBank: MN996532), [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273" href="/article/10.1007/s10930-020-09901-4#ref-CR13" id="ref-link-section-d447967688e381">13</a>] which was isolated from horseshoe bats [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 14" title="Cagliani R, Forni D, Clerici M, Sironi M (2020) Computational inference of selection underlying the evolution of the novel coronavirus, SARS-CoV-2. J Virol. 
 https://doi.org/10.1128/JVI.00411-20
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR14" id="ref-link-section-d447967688e384">14</a>].</p></div></div></section><section data-title="Discussion: Proteins of SARS CoV-2"><div class="c-article-section" id="Sec2-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec2"><span class="c-article-section__title-number">2 </span>Discussion: Proteins of SARS CoV-2</h2><div class="c-article-section__content" id="Sec2-content"><p>SARS CoV-2 (NC_045512.2) has a total of 11 genes with 11 open reading frames (ORFs) (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab1">1</a>): ORF1ab, ORF2 (Spike protein), ORF3a, ORF4 (Envelope protein), ORF5 (Membrane protein), ORF6, ORF7a, ORF7b, ORF8, ORF9 (Nucleocapsid protein), and ORF10.</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-1"><figure><figcaption class="c-article-table__figcaption"><b id="Tab1" data-test="table-caption">Table 1 The genes expressed by SARS CoV-2 (NC_045512.2)</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s10930-020-09901-4/tables/1" aria-label="Full size table 1"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec3"><span class="c-article-section__title-number">2.1 </span>Polyprotein Expressed by ORF1ab</h3><p>The first gene (ORF1ab) expresses a polyprotein. The ORF1ab polyprotein is comprised of 16 nonstructural proteins (NSPs) (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab2">2</a>).</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-2"><figure><figcaption class="c-article-table__figcaption"><b id="Tab2" data-test="table-caption">Table 2 The nonstructural proteins (NSPs) found in the polyprotein of SARS CoV-2</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s10930-020-09901-4/tables/2" aria-label="Full size table 2"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec4"><span class="c-article-section__title-number">2.1.1 </span>NSP1 (Leader Protein)</h4><p>Nonstructural protein 1 (NSP1) is the first protein of the polyprotein of SARS CoV-2 (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig1">1</a>—sequence alignment of NSP1 for SARS CoV with SARS CoV-2). This protein is also known as the leader protein. This protein is also found in SARS coronavirus and is known to be a potent inhibitor of host gene expression. NSP1 binds to the 40S ribosome of the host cell to inactivate translation and promotes host mRNA degradation selectively, while the viral SARS CoV mRNA remain intact [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S (2011) SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLoS Pathog 7:e1002433" href="/article/10.1007/s10930-020-09901-4#ref-CR15" id="ref-link-section-d447967688e1428">15</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig1">1</a> shows the amino acid sequence alignment for the NSP1 proteins of SARS CoV (from genome: NCBI Reference Sequence: NC_004718.3) and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-1" data-title="Fig. 1"><figure><figcaption><b id="Fig1" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 1</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/1" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig1_HTML.png?as=webp"><img aria-describedby="Fig1" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig1_HTML.png" alt="figure 1" loading="lazy" width="685" height="101"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-1-desc"><p>Alignment of the primary amino acid sequence of NSP1 of SARS CoV (top, NP_828860.2) and SARS CoV-2 (YP_009725297.1). Sequence identity: 84.4%. Sequence similarity: 93.9%—determined using LALIGN software (and for subsequent alignments, Figs. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig2">2</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig3">3</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig4">4</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig5">5</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig6">6</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig7">7</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig8">8</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig9">9</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig10">10</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig11">11</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig12">12</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig13">13</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig14">14</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig15">15</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig16">16</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig17">17</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig18">18</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig19">19</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig20">20</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig21">21</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig22">22</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig23">23</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig24">24</a>, <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig25">25</a>, and <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig26">26</a>, see Supporting Information for output data) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 16" title="Madeira F, Park YM, Lee J, Buso N, Gur T, Madhusoodanan N, Basutkar P, Tivey ARN, Potter SC, Finn RD, Lopez R (2019) The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res 47:W636–W641" href="/article/10.1007/s10930-020-09901-4#ref-CR16" id="ref-link-section-d447967688e1523">16</a>].</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/1" data-track-dest="link:Figure1 Full size image" aria-label="Full size image figure 1" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-2" data-title="Fig. 2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 2</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/2" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig2_HTML.png?as=webp"><img aria-describedby="Fig2" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig2_HTML.png" alt="figure 2" loading="lazy" width="685" height="254"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-2-desc"><p>The primary amino acid sequence alignment of NSP2 for SARS CoV (NP_828861.2) and SARS CoV-2 (YP_009725298.1). These proteins have 68.3% sequence identity (90.0% similar)</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/2" data-track-dest="link:Figure2 Full size image" aria-label="Full size image figure 2" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec5"><span class="c-article-section__title-number">2.1.2 </span>NSP2</h4><p>Nonstructural protein 2 (NSP2) is the second protein of the polyprotein of SARS CoV-2 (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig2">2</a>). This protein is conserved in SARS CoV, the related beta coronavirus to SARS CoV-2. In SARS CoV, NSP2 was found to bind to two host proteins: prohibitin 1 and prohibitin 2 (PHB1 and PHB2) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 17" title="Cornillez-Ty CT, Liao L, Yates JR, Kuhn P, Buchmeier MJ (2009) Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. J Virol 83:10314–10318" href="/article/10.1007/s10930-020-09901-4#ref-CR17" id="ref-link-section-d447967688e1562">17</a>]. PHB1 and PHB2 proteins are known to play roles in cell cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. The binding of NSP2 to PHB1 and PHB2 proteins suggest that NSP2 plays a role in disrupting the host cell environment.</p><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec6"><span class="c-article-section__title-number">2.1.3 </span>NSP3 (Papain like Proteinase)</h4><p>NSP3 is the papain-like proteinase protein (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig3">3</a>). This protein is nearly 200 kDa in size and is the largest protein (not including the polyproteins ORF1a and ORF1ab) encoded by the coronaviruses. With such a long sequence, it possesses several conserved domains: ssRNA binding, ADPr binding, G-quadruplex binding, ssRNA binding, protease (papain-like protease), and NSP4 binding), and transmembrane domain. Among the 16 nonstructural proteins, NSP3, NSP4, and NSP6 have transmembrane domains [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Sakai Y, Kawachi K, Terada Y, Omori H, Matsuura Y, Kamitani W (2017) Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication. Virology 510:165–174" href="/article/10.1007/s10930-020-09901-4#ref-CR18" id="ref-link-section-d447967688e1576">18</a>]. The papain like protease 1 (PL1 protease) of alpha coronavirus (alpha CoV) Transmissible Gastroenteritis Virus (TGEV), which is part of NSP3, was shown to cleave the site between NSP2 and NSP3. Furthermore, this papain like protease domain is responsible for the release of NSP1, NSP2, and NSP3 from the N-terminal region of polyproteins 1a and 1ab from coronaviruses [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 19" title="Lei J, Kusov Y, Hilgenfeld R (2018) Nsp3 of coronaviruses: structures and functions of a large multi-domain protein. Antiviral Res 149:58–74" href="/article/10.1007/s10930-020-09901-4#ref-CR19" id="ref-link-section-d447967688e1579">19</a>]. Considering this important protease activity to release essential proteins for viral activity, the inhibition of NSP3 protease activity is an important target for antiviral activity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Baez-Santos YM, St. John SE, Mesecar AD (2015) The SARS-coronavirus papain-like protease: structure, function, and inhibition by designed antiviral compounds. Antiviral Res 115:21–38" href="/article/10.1007/s10930-020-09901-4#ref-CR20" id="ref-link-section-d447967688e1582">20</a>]. Tanshinones, a class of natural products have been found to inhibit NSP3 protease activity.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3" data-title="Fig. 3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 3</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/3" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig3_HTML.png?as=webp"><img aria-describedby="Fig3" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig3_HTML.png" alt="figure 3" loading="lazy" width="685" height="879"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-3-desc"><p>The primary amino acid sequence alignment of NSP3 for SARS CoV (NP_828862.2) and SARS CoV-2 (YP_009725299.1). Sequence identity: 76.0%, sequence similarity: 91.8%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/3" data-track-dest="link:Figure3 Full size image" aria-label="Full size image figure 3" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec7"><span class="c-article-section__title-number">2.1.4 </span>NSP4 (Contains Transmembrane Domain 2)</h4><p>NSP4 interacts with NSP3 and possibly host proteins to confer a role related to membrane rearrangement in SARS CoV. Moreover, the interaction between NSP4 and NSP3 is essential for viral replication [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Sakai Y, Kawachi K, Terada Y, Omori H, Matsuura Y, Kamitani W (2017) Two-amino acids change in the nsp4 of SARS coronavirus abolishes viral replication. Virology 510:165–174" href="/article/10.1007/s10930-020-09901-4#ref-CR18" id="ref-link-section-d447967688e1611">18</a>]. The sequence alignment for NSP4 proteins for SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig4">4</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-4" data-title="Fig. 4"><figure><figcaption><b id="Fig4" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 4</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/4" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig4_HTML.png?as=webp"><img aria-describedby="Fig4" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig4_HTML.png" alt="figure 4" loading="lazy" width="685" height="246"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-4-desc"><p>The primary amino acid sequence alignment of NSP4 for SARS CoV (NP_904322.1) and SARS CoV-2 (YP_009725300.1). Sequence identity: 80.0%, sequence similarity: 95.0%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/4" data-track-dest="link:Figure4 Full size image" aria-label="Full size image figure 4" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec99"><span class="c-article-section__title-number">2.1.5 </span>NSP5 (3C-like proteinase)</h4><p>The NSP5 protein based on the Middle East Respiratory Syndrome (MERS) coronavirus has been characterized. NSP5 cleaves at 11 distinct sites to yield mature and intermediate nonstructural proteins (NSPs) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 21" title="Tomar S, Johnston ML, St. John SE, Osswald HL, Nyalapatla PR, Paul LN, Ghosh AK, Denison MR, Mesecar AD (2015) Ligand-induced dimerization of middle east respiratory syndrome (MERS) coronavirus nsp5 protease (3CLpro) implications For nsp5 Regulation And The Development Of Antivirals. J. Biol. Chem. 290:19403–19422" href="/article/10.1007/s10930-020-09901-4#ref-CR21" id="ref-link-section-d447967688e1642">21</a>]. The amino acid sequence alignment for NSP5 of SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig5">5</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-5" data-title="Fig. 5"><figure><figcaption><b id="Fig5" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 5</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/5" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig5_HTML.png?as=webp"><img aria-describedby="Fig5" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig5_HTML.png" alt="figure 5" loading="lazy" width="685" height="135"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-5-desc"><p>The primary amino acid sequence of NSP5 for SARS CoV (NP_828863.1) and SARS CoV-2 (YP_009725301.1). Sequence identity: 96.1%, sequence similarity: 99.7%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/5" data-track-dest="link:Figure5 Full size image" aria-label="Full size image figure 5" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec8"><span class="c-article-section__title-number">2.1.6 </span>NSP6 (Putative Transmembrane Domain)</h4><p>The NSP6 protein of the avian coronavirus (infectious bronchitis virus, IBV) was shown to generate autophagosomes from the endoplasmic reticulum (ER) (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig6">6</a>b shows sequence alignment with SARS CoV-2 NSP6). Autophagosomes facilitate assembly of replicase proteins. Furthermore, NSP6 limited autophagosome/lysosome expansion, which in turn prevents autophagosomes from delivering viral components for degradation in lysosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Cottam EM, Whelband MC, Wileman T (2014) Coronavirus NSP6 restricts autophagosome expansion. Autophagy 10:1426–1441" href="/article/10.1007/s10930-020-09901-4#ref-CR22" id="ref-link-section-d447967688e1676">22</a>]. With SARS CoV, NSP6 was shown to induce membrane vesicles [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 23" title="Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ (2013) Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio 13:e00524–e1513" href="/article/10.1007/s10930-020-09901-4#ref-CR23" id="ref-link-section-d447967688e1679">23</a>]. The amino acid sequence alignment for NSP6 of SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig6">6</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-6" data-title="Fig. 6"><figure><figcaption><b id="Fig6" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 6</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/6" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig6_HTML.png?as=webp"><img aria-describedby="Fig6" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig6_HTML.png" alt="figure 6" loading="lazy" width="685" height="136"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-6-desc"><p>Amino acid sequence alignment between the NSP6 proteins of SARS CoV (top: NP_828864.1) and SARS-CoV-2 (bottom: YP_009725302.1). Sequence identity: 88.2%, sequence similarity: 98.3%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/6" data-track-dest="link:Figure6 Full size image" aria-label="Full size image figure 6" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec9"><span class="c-article-section__title-number">2.1.7 </span>NSP7</h4><p>NSP7 is required to form a complex with NSP8 (next section) and NSP12 to yield the RNA polymerase activity of NSP8 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 24" title="te Velthuis AJ, van de Worm SH, Snijder EJ (2012) The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res 40:1737–1747" href="/article/10.1007/s10930-020-09901-4#ref-CR24" id="ref-link-section-d447967688e1710">24</a>]. The primary amino acid sequence alignment for the NSP8 proteins for SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig7">7</a>. Only one amino acid residue is different (arginine vs. lysine) but the charge is conserved at this location.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-7" data-title="Fig. 7"><figure><figcaption><b id="Fig7" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 7</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/7" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig7_HTML.png?as=webp"><img aria-describedby="Fig7" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig7_HTML.png" alt="figure 7" loading="lazy" width="685" height="66"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-7-desc"><p>The primary amino acid sequence alignment of NSP7 SARS CoV (NP_828865.1) and SARS CoV-2 (YP_009725303.1). Sequence identity: 98.8%, sequence similarity: 100%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/7" data-track-dest="link:Figure7 Full size image" aria-label="Full size image figure 7" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec10"><span class="c-article-section__title-number">2.1.8 </span>NSP8</h4><p>NSP8 is a peptide cofactor that makes a heterodimer with NSP7 (the other peptide cofactor), and this NSP7-NSP8 heterodimer complexes with NSP12. In addition to the NSP7-NSP8 heterodimer, an NSP8 monomer unit also complexes with NSP12, which ultimately forms the RNA polymerase complex. The cryo-EM structure of this complex has been solved [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q, Lou Z, Rao Z (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 
 https://doi.org/10.1126/science.abb7498
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR25" id="ref-link-section-d447967688e1741">25</a>]. The amino acid sequence alignment for NSP8 of SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig8">8</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-8" data-title="Fig. 8"><figure><figcaption><b id="Fig8" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 8</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/8" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig8_HTML.png?as=webp"><img aria-describedby="Fig8" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig8_HTML.png" alt="figure 8" loading="lazy" width="685" height="101"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-8-desc"><p>The primary amino acid sequence alignment of NSP8 for SARS CoV (NP_828866.1) and SARS CoV-2 (YP_009725304.1). Sequence identity: 97.5%, sequence similarity: 100.0%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/8" data-track-dest="link:Figure8 Full size image" aria-label="Full size image figure 8" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec11"><span class="c-article-section__title-number">2.1.9 </span>NSP9</h4><p>NSP9 from the porcine reproductive and respiratory syndrome virus (PRRSV) has been found to interact with the DEAD-box RNA helicase 5 (DDX5) cellular protein [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 26" title="Zhao S, Ge X, Wang X, Liu A, Guo X, Zhou L, Yu K, Yang H (2015) The DEAD-box RNA helicase 5 positively regulates the replication of porcine reproductiv e and respiratory syndrome virus by interacting with viral Nsp9 in vitro. Virus Res 195:217–224" href="/article/10.1007/s10930-020-09901-4#ref-CR26" id="ref-link-section-d447967688e1772">26</a>]. This interaction between NSP9 and DDX5 has been shown to be important for viral replication—when the DDX5 gene was silenced in MARC-145 cells, the virus titers were lower by tenfold. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig9">9</a> shows the amino acid sequence alignment between the two NSP9 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-9" data-title="Fig. 9"><figure><figcaption><b id="Fig9" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 9</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/9" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig9_HTML.png?as=webp"><img aria-describedby="Fig9" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig9_HTML.png" alt="figure 9" loading="lazy" width="685" height="66"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-9-desc"><p>The primary amino acid sequence alignment of NSP9 for SARS CoV (NP_828868.1) and SARS CoV-2 (YP_009725305.1). Sequence identity: 97.3%, sequence similarity: 99.1%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/9" data-track-dest="link:Figure9 Full size image" aria-label="Full size image figure 9" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec12"><span class="c-article-section__title-number">2.1.10 </span>NSP10</h4><p>NSP10 has been shown to interact with NSP14 in SARS coronavirus, and this interaction stimulates activity of NSP14. NSP 14 is known to function as an S-adenosylmethionine (SAM)-dependent (guanine-N7) methyl transferase (N7-MTase) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 27" title="Ma Y, Wu L, Shaw N, Gao Y, Wang J, Sun Y, Lou Z, Yan L, Zhang R, Rao Z (2015) Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex. Proc Natl Acad Sci USA 112:9436–9441" href="/article/10.1007/s10930-020-09901-4#ref-CR27" id="ref-link-section-d447967688e1804">27</a>]. Furthermore, NSP10 has also been shown to stimulate the activity of NSP16, which is a 2′-O-methyltransferase [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 28" title="Wang Y, Sun Y, Wu A, Xu S, Pan R, Zeng C, Jin X, Ge X, Shi Z, Ahola T, Guo D (2015) Coronavirus nsp10/nsp16 methyltransferase can be targeted by nsp10-derived peptide in vitro and in vivo to reduce replication and pathogenesis. J Virol 89:8416–8427" href="/article/10.1007/s10930-020-09901-4#ref-CR28" id="ref-link-section-d447967688e1807">28</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig10">10</a> shows the amino acid sequence alignment between the two NSP10 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-10" data-title="Fig. 10"><figure><figcaption><b id="Fig10" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 10</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/10" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig10_HTML.png?as=webp"><img aria-describedby="Fig10" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig10_HTML.png" alt="figure 10" loading="lazy" width="685" height="66"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-10-desc"><p>The primary amino acid sequence alignment of NSP10 for SARS CoV (NP_828868.1) and SARS CoV-2 (YP_009725306.1). Sequence identity: 97.1%, sequence similarity: 99.3%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/10" data-track-dest="link:Figure10 Full size image" aria-label="Full size image figure 10" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec13"><span class="c-article-section__title-number">2.1.11 </span>NSP11</h4><p>The function of NSP11 seems to be unknown. NSP11 is made of thirteen amino acids and the first nine amino acids (sadaqsfln) are identical to the first nine in NSP12. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig11">11</a> shows the amino acid sequence alignment between the two NSP12 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-11" data-title="Fig. 11"><figure><figcaption><b id="Fig11" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 11</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/11" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig11_HTML.png?as=webp"><img aria-describedby="Fig11" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig11_HTML.png" alt="figure 11" loading="lazy" width="685" height="53"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-11-desc"><p>The primary amino acid sequence alignment of NSP11 for SARS CoV (NP_904321.1) and SARS CoV-2 (YP_009725312.1). Sequence identity: 84.6%, sequence similarity: 100.0%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/11" data-track-dest="link:Figure11 Full size image" aria-label="Full size image figure 11" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec14"><span class="c-article-section__title-number">2.1.12 </span>NSP12 (RNA Dependent RNA Polymerase)</h4><p>NSP12 is the RNA-dependent RNA polymerase that copies viral RNA. As mentioned, NSP12 makes a complex with an NSP7-NSP8 heterodimer and an NSP8 monomer to confer processivity of NSP12. NSP12 exhibits poor processivity in RNA synthesis—that is the presence of NSP7 and NSP8 lowers the dissociation rate of NSP12 from RNA [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 29" title="Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE, Decroly E, Snijder EJ, Canard B, Imbert I (2014) One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci USA 111:E3900–E3909" href="/article/10.1007/s10930-020-09901-4#ref-CR29" id="ref-link-section-d447967688e1866">29</a>]. The amino acid sequence alignment between the two NSP12 proteins from SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig12">12</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-12" data-title="Fig. 12"><figure><figcaption><b id="Fig12" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 12</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/12" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig12_HTML.png?as=webp"><img aria-describedby="Fig12" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig12_HTML.png" alt="figure 12" loading="lazy" width="685" height="426"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-12-desc"><p>The primary amino acid sequence alignment of NSP12 for SARS CoV (NP_828869.1) and SARS CoV-2 (YP_009725307.1). Sequence identity: 96.4%, sequence similarity: 99.4%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/12" data-track-dest="link:Figure12 Full size image" aria-label="Full size image figure 12" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec15"><span class="c-article-section__title-number">2.1.13 </span>NSP13 (Helicase)</h4><p>SARS CoV was used to characterize the helicase enzyme, NSP13, which unwinds duplex RNA [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 30" title="Jang K-J, Jeong S, Kang DY, Sp N, Yang YM, Kim D-E (2020) A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA. Sci Rep 10:4481" href="/article/10.1007/s10930-020-09901-4#ref-CR30" id="ref-link-section-d447967688e1897">30</a>]. The crystal structure of NSP13 of SARS CoV has been reported [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 31" title="Jia Z, Yan L, Ren Z, Wu L, Wang J, Guo J, Zheng L, Ming Z, Zhang L, Lou Z, Rao Z (2019) Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res 47:6538–6550" href="/article/10.1007/s10930-020-09901-4#ref-CR31" id="ref-link-section-d447967688e1900">31</a>]. Furthermore, it has been shown that binding of NSP12 with NSP13 can enhance the helicase activity of NSP13. In addition to its helicase activity, NSP13 of SARS CoV is also known to possess 5′-triphosphatase activity, which is responsible for introducing the 5′-terminal cap of the viral mRNA [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 32" title="Ivanov KA, Thiel V, Dobbe JC, van der Meer Y, Snijder EJ, Ziebuhr J (2004) Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol 78:5619–5632" href="/article/10.1007/s10930-020-09901-4#ref-CR32" id="ref-link-section-d447967688e1903">32</a>]. Both eukaryotic and most viral mRNA have a 5′-terminal cap structure: m7G(5)ppp(5)N-. This 5′-terminal cap is the site of recognition for translation and plays a role in splicing, nuclear export, translation, and stability of mRNA. This process of incorporating the 5′-terminal cap will be discussed in the next section: (xiv) NSP14. The sequence alignment for NSP13 of SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig13">13</a>. Interestingly, only one amino acid residue is different out of the 601 amino acids in these two proteins (isoleucine vs. valine).</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-13" data-title="Fig. 13"><figure><figcaption><b id="Fig13" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 13</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/13" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig13_HTML.png?as=webp"><img aria-describedby="Fig13" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig13_HTML.png" alt="figure 13" loading="lazy" width="685" height="281"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-13-desc"><p>The primary amino acid sequence of NSP13 SARS CoV (NP_828870.1) and SARS CoV-2 (YP_009725308.1). Sequence identity: 99.8%, sequence similarity: 100.0%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/13" data-track-dest="link:Figure13 Full size image" aria-label="Full size image figure 13" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec16"><span class="c-article-section__title-number">2.1.14 </span>NSP14 (3′ to 5′ Endonuclease, N7-Methyltransferase)</h4><p>NSP14 from coronavirus is known to have 3′-5′ exoribonuclease activity and N7-methyltransferase activity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 33" title="Case JB, Ashbrook AW, Dermody TS, Denison MR (2016) Mutagenesis of S-adenosyl-l-methionine-binding residues in coronavirus nsp14 N7-methyltransferase demonstrates differing requirements for genome translation and resistance to innate immunity. J Virol 90:7248–7256" href="/article/10.1007/s10930-020-09901-4#ref-CR33" id="ref-link-section-d447967688e1934">33</a>]. The guanine-N7-methyltransferase activity is part of the process for introducing the 5′-cap of the virus, which involves multiple steps: [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Li X, Zai J, Wang X, Li Y (2020) Potential of large “first generation” human-to-human transmission of 2019-nCoV. J Med Virol 92:448–454" href="/article/10.1007/s10930-020-09901-4#ref-CR1" id="ref-link-section-d447967688e1937">1</a>] the gamma-phosphate of the 5′end of nascent mRNA is removed by the RNA triphosphatase (NSP13), [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 32" title="Ivanov KA, Thiel V, Dobbe JC, van der Meer Y, Snijder EJ, Ziebuhr J (2004) Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol 78:5619–5632" href="/article/10.1007/s10930-020-09901-4#ref-CR32" id="ref-link-section-d447967688e1940">32</a>], [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Gralinski LE, Menachery VD (2020) Return of the Coronavirus: 2019-nCoV. Viruses 12:135" href="/article/10.1007/s10930-020-09901-4#ref-CR2" id="ref-link-section-d447967688e1943">2</a>] a GMP moiety derived from a covalent enzyme-GMP intermediate is transferred to the resulting mRNA with a diphosphate end, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen K-Y (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 9:221–236" href="/article/10.1007/s10930-020-09901-4#ref-CR3" id="ref-link-section-d447967688e1946">3</a>] the GpppA cap is methylated with S-adenosyl-methionine, which is catalyzed by the guanine-N7-methyltransferase (NSP14) to yield the cap-0 structure, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 34" title="Jin X, Chen Y, Sun Y, Zeng C, Wang Y, Tao J, Wu A, Yu X, Zhang Z, Tian J, Guo D (2013) Characterization of the guanine-N7 methyltransferase activity of coronavirus nsp14 on nucleotide GTP. Virus Res 176:45–52" href="/article/10.1007/s10930-020-09901-4#ref-CR34" id="ref-link-section-d447967688e1950">34</a>] and [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, Zhang Z (2020) The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol 92:667–674" href="/article/10.1007/s10930-020-09901-4#ref-CR4" id="ref-link-section-d447967688e1953">4</a>] 2′-O-methylation by NSP16 of adenine gives the cap-1 structure [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 35" title="Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder EJ, Canard B, Decroly E (2010) In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog 6:e1000863" href="/article/10.1007/s10930-020-09901-4#ref-CR35" id="ref-link-section-d447967688e1956">35</a>]. It is currently unknown which enzyme incorporates the GMP group involved in the second step, and it is possible that the virus uses the host guanylyltransferase enzyme [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 36" title="Nakagawa K, Lokugamage KG, Makino S (2016) Viral and cellular mRNA translation in coronavirus-infected cells. Adv Virus Res 96:165–192" href="/article/10.1007/s10930-020-09901-4#ref-CR36" id="ref-link-section-d447967688e1959">36</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig14">14</a> shows the amino acid sequence alignment between the NSP14 proteins of SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-14" data-title="Fig. 14"><figure><figcaption><b id="Fig14" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 14</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/14" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig14_HTML.png?as=webp"><img aria-describedby="Fig14" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig14_HTML.png" alt="figure 14" loading="lazy" width="685" height="246"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-14-desc"><p>The primary amino acid sequence alignment of NSP14 of SARS CoV (NP_828871.1) and SARS CoV-2(YP_009725309.1). Sequence identity: 95.1%, sequence similarity: 99.1%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/14" data-track-dest="link:Figure14 Full size image" aria-label="Full size image figure 14" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec17"><span class="c-article-section__title-number">2.1.15 </span>NSP15 (endoRNAse)</h4><p>NSP15 of SARS coronavirus has been biochemically characterized as an endoribonuclease that cleaves RNA at uridylates at the 3′-position to form a 2′-3′ cyclic phosphodiester product [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 37" title="Bhardwaj K, Sun J, Holzenburg A, Guarino LA, Kao CC (2006) RNA recognition and cleavage by the SARS coronavirus endoribonuclease. J Mol Biol 361:243–256" href="/article/10.1007/s10930-020-09901-4#ref-CR37" id="ref-link-section-d447967688e1990">37</a>]. The NSP15 protein specifically targets and degrades the viral polyuridine sequences to prevent the host immune sensing system from detecting the virus [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 38" title="Hackbart M, Deng X, Baker SC (2020) Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors. Proc Natl Acad Sci USA 117:8094–8103" href="/article/10.1007/s10930-020-09901-4#ref-CR38" id="ref-link-section-d447967688e1993">38</a>]. The crystal structure of NSP15 has been reported for SARS CoV [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 39" title="Bhardwaj K, Palaninathan S, Ortiz Alcantara JM, Li Yi L, Guarino L, Sacchettini JC, Cheng Kao C (2008) Structural and functional analyses of the severe acute respiratory syndrome coronavirus endoribonuclease Nsp15. J Biol Chem 283:3655–3664" href="/article/10.1007/s10930-020-09901-4#ref-CR39" id="ref-link-section-d447967688e1996">39</a>] and SARS CoV-2 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 40" title="Kim Y, Jedrzejczak R, Maltseva NI, Wilamowski M, Endres M, Godzik A, Michalska K, Joachimiak A (2020) Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2. Protein Sci. 
 https://doi.org/10.1002/pro.3873
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR40" id="ref-link-section-d447967688e1999">40</a>]. NSP15 uses manganese as a cofactor to promote endoribonuclease activity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 41" title="Bhardwaj K, Guarino L, Kao CC (2004) The severe acute respiratory syndrome coronavirus Nsp15 protein is an endoribonuclease that prefers manganese as a cofactor. J Virol 78:12218" href="/article/10.1007/s10930-020-09901-4#ref-CR41" id="ref-link-section-d447967688e2002">41</a>]. It has been suggested that NSP15 degrades viral dsRNA to prevent host recognition [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 42" title="Deng X, Baker SC (2018) An “Old” protein with a new story: coronavirus endoribonuclease is important for evading host antiviral defenses. Virology 517:157–163" href="/article/10.1007/s10930-020-09901-4#ref-CR42" id="ref-link-section-d447967688e2006">42</a>]. The amino acid sequence alignment of NSP15 from SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig15">15</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-15" data-title="Fig. 15"><figure><figcaption><b id="Fig15" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 15</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/15" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig15_HTML.png?as=webp"><img aria-describedby="Fig15" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig15_HTML.png" alt="figure 15" loading="lazy" width="685" height="173"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-15-desc"><p>The primary amino acid sequence alignment of NSP15 of SARS CoV (NP_828872.1) and SARS CoV-2 (YP_009725310.1). Sequence identity: 88.7%, sequence similarity: 97.7%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/15" data-track-dest="link:Figure15 Full size image" aria-label="Full size image figure 15" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h4 class="c-article__sub-heading c-article__sub-heading--small" id="Sec18"><span class="c-article-section__title-number">2.1.16 </span>NSP16 (2′-O-Ribose-Methyltransferase)</h4><p>NSP16 for coronavirus has been biochemically [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 43" title="Decroly E, Imbert I, Coutard B, Bouvet M, Selisko B, Alvarez K, Gorbalenya AE, Snijder EJ, Canard B (2008) Coronavirus nonstructural protein 16 Is a cap-0 binding enzyme possessing (nucleoside-2’O)-methyltransferase activity. J Virol 82:8071–8084" href="/article/10.1007/s10930-020-09901-4#ref-CR43" id="ref-link-section-d447967688e2038">43</a>] (feline coronavirus, FCoV) and structurally [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 44" title="Decroly E, Debarnot C, Ferron F, Bouvet M, Coutard B, Imbert I, Gluais L, Papageorgiou N, Sharff A, Bricogne G, Ortiz-Lombardia M, Lescar J, Canard B (2011) Crystal structure and functional analysis of the sars-coronavirus RNA cap 2’-O-methyltransferase nsp10/nsp16 complex. PLoS Pathog 7:e1002059" href="/article/10.1007/s10930-020-09901-4#ref-CR44" id="ref-link-section-d447967688e2041">44</a>] (complex of NSP10-NSP16 for SARS CoV) characterized. The viral RNA has a 5′-cap, which protects it from mRNA degradation by 5′-exoribonucleases, promotes mRNA translation, and prevents the viral RNA from being recognized by innate immunity mechanisms [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 44" title="Decroly E, Debarnot C, Ferron F, Bouvet M, Coutard B, Imbert I, Gluais L, Papageorgiou N, Sharff A, Bricogne G, Ortiz-Lombardia M, Lescar J, Canard B (2011) Crystal structure and functional analysis of the sars-coronavirus RNA cap 2’-O-methyltransferase nsp10/nsp16 complex. PLoS Pathog 7:e1002059" href="/article/10.1007/s10930-020-09901-4#ref-CR44" id="ref-link-section-d447967688e2044">44</a>]. The RNA cap is an N7-methylated guanine nucleotide connected through a 5′-5′ triphosphate bridge to the first transcribed nucleotide (adenine). NSP16 methylates the 2′-hydroxy group of adenine using S-adenosylmethionine as the methyl source. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig16">16</a> shows the amino acid sequence alignment between the two NSP16 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-16" data-title="Fig. 16"><figure><figcaption><b id="Fig16" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 16</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/16" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig16_HTML.png?as=webp"><img aria-describedby="Fig16" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig16_HTML.png" alt="figure 16" loading="lazy" width="685" height="136"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-16-desc"><p>The primary amino acid sequence alignment of NSP16 of SARS CoV (NP_828873.2) and SARS CoV-2 (YP_009725311.1). Sequence identity: 93.3%, sequence similarity: 99.0%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/16" data-track-dest="link:Figure16 Full size image" aria-label="Full size image figure 16" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec19"><span class="c-article-section__title-number">2.2 </span>Spike Protein (Surface Glycoprotein)</h3><p>The spike protein (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig17">17</a>—sequence alignment between SARS CoV and SARS CoV-2) is a glycoprotein, which mediates attachment of the virus to the host cell. The structure of the spike (S) protein has been determined. This protein recognizes the human angiotensin-converting enzyme 2 (ACE2) protein on the host cell surface [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L, Wang X (2020) Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 
 https://doi.org/10.1038/s41586-020-2180-5s
 
 
" href="#ref-CR45" id="ref-link-section-d447967688e2079">45</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F (2020) Structural basis of receptor recognition by SARS-CoV-2. Nature. 
 https://doi.org/10.1038/s41586-020-2179-y
 
 
" href="#ref-CR46" id="ref-link-section-d447967688e2079_1">46</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 47" title="Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Vessler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 180:281–292" href="/article/10.1007/s10930-020-09901-4#ref-CR47" id="ref-link-section-d447967688e2082">47</a>]. SARS CoV spike mouse polyclonal antibodies potently inhibited SARS CoV-2 spike protein mediated entry into cells [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 47" title="Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Vessler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 180:281–292" href="/article/10.1007/s10930-020-09901-4#ref-CR47" id="ref-link-section-d447967688e2085">47</a>]. Interestingly, a furin cleavage site (highlighted in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig17">17</a>: QTQTNSPRRARSVASQSIIA) was located in the S protein of SARS CoV-2, which was lacking in the S protein of SARS CoV. This difference in site could possibly explain the difference in pathogenicity of these two viruses [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 47" title="Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Vessler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 180:281–292" href="/article/10.1007/s10930-020-09901-4#ref-CR47" id="ref-link-section-d447967688e2092">47</a>].</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-17" data-title="Fig. 17"><figure><figcaption><b id="Fig17" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 17</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/17" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig17_HTML.png?as=webp"><img aria-describedby="Fig17" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig17_HTML.png" alt="figure 17" loading="lazy" width="685" height="531"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-17-desc"><p>The primary amino acid sequence alignment of the spike proteins from SARS CoV (NP_828851.1) and SARS CoV-2 (BCA87361.1). Sequence identity: 76.0%, sequence similarity: 91.5%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/17" data-track-dest="link:Figure17 Full size image" aria-label="Full size image figure 17" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec20"><span class="c-article-section__title-number">2.3 </span>ORF3a Protein</h3><p>The ORF3a protein from SARS CoV is an ion channel protein related to NLRP3 inflammasome activation. ORF3a interacts with TRAF3, which in turn activates ASC ubiquitination, and as a result, leads to activation of caspase 1 and IL-1β maturation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 48" title="Siu K-L, Yuen K-S, Castano-Rodriguez C, Ye Z-W, Yeung M-L, Fung S-Y, Yuan S, Chan C-P, Yuen K-Y, Enjuanes L, Jin D-Y (2019) Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J 33:8865–8877" href="/article/10.1007/s10930-020-09901-4#ref-CR48" id="ref-link-section-d447967688e2120">48</a>]. The amino acid sequence alignment between the two ORF3a proteins from SARS CoV and SARS CoV-2 is shown in Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig18">18</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-18" data-title="Fig. 18"><figure><figcaption><b id="Fig18" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 18</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/18" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig18_HTML.png?as=webp"><img aria-describedby="Fig18" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig18_HTML.png" alt="figure 18" loading="lazy" width="685" height="141"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-18-desc"><p>The primary amino acid sequence alignment of the ORF3a proteins from SARS CoV (NP_828852.2) and SARS CoV-2 (BCA87362.1). Sequence identity: 72.4%, sequence similarity: 90.2%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/18" data-track-dest="link:Figure18 Full size image" aria-label="Full size image figure 18" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec21"><span class="c-article-section__title-number">2.4 </span>Envelope Protein</h3><p>The envelope protein is a small integral membrane protein in coronaviruses, which can oligomerize and create an ion channel [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 49" title="Verdia-Baguena C, Nieto-Torres JL, Alcaraz A, DeDiego ML, Torres J, Aguilella VM, Enjuanes L (2012) Coronavirus E protein forms ion channels with functionally and structurally-involved membrane lipids. Virology 432:485–494" href="/article/10.1007/s10930-020-09901-4#ref-CR49" id="ref-link-section-d447967688e2152">49</a>]. The four structural proteins of coronaviruses are: S protein, M protein, E protein, and N protein [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 50" title="Schoeman D, Fielding BC (2019) Coronavirus envelope protein: current knowledge. Virol J 16:69" href="/article/10.1007/s10930-020-09901-4#ref-CR50" id="ref-link-section-d447967688e2155">50</a>]. The E protein has been shown to play multiple roles in the viral replication cycle: [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Li X, Zai J, Wang X, Li Y (2020) Potential of large “first generation” human-to-human transmission of 2019-nCoV. J Med Virol 92:448–454" href="/article/10.1007/s10930-020-09901-4#ref-CR1" id="ref-link-section-d447967688e2158">1</a>] viral assembly, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 51" title="Lim KP, Liu DX (2001) The Missing Link in Coronavirus Assembly retention of the avian coronavirus infectious bronchitis virus envelope protein in the pre-golgi compartments and physical interaction between the envelope and membrane proteins. J Biol Chem 276:17515–17523" href="/article/10.1007/s10930-020-09901-4#ref-CR51" id="ref-link-section-d447967688e2161">51</a>] [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Gralinski LE, Menachery VD (2020) Return of the Coronavirus: 2019-nCoV. Viruses 12:135" href="/article/10.1007/s10930-020-09901-4#ref-CR2" id="ref-link-section-d447967688e2164">2</a>] virion release, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 52" title="Ruch TR, Machamer CE (2012) The coronavirus E protein: assembly and beyond. Viruses 4:363–382" href="/article/10.1007/s10930-020-09901-4#ref-CR52" id="ref-link-section-d447967688e2168">52</a>] and [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen K-Y (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 9:221–236" href="/article/10.1007/s10930-020-09901-4#ref-CR3" id="ref-link-section-d447967688e2171">3</a>] viral pathogenesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 53" title="Weiss SR, Navas-Martin S (2005) Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69:635–664" href="/article/10.1007/s10930-020-09901-4#ref-CR53" id="ref-link-section-d447967688e2174">53</a>]. Interestingly, in the sequence alignment of the E proteins from SARS CoV and SARS CoV-2 (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig19">19</a>), there is a glutamate residue (E69) with a negative charge in SARS CoV that corresponds to a positively charged arginine in SARS CoV-2 (R69).</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-19" data-title="Fig. 19"><figure><figcaption><b id="Fig19" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 19</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/19" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig19_HTML.png?as=webp"><img aria-describedby="Fig19" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig19_HTML.png" alt="figure 19" loading="lazy" width="685" height="29"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-19-desc"><p>The primary amino acid sequence of the E proteins (ORF4) from SARS CoV (NP_828854.1) and SARS CoV-2 (BCA87363.1). Sequence identity: 94.7%, sequence similarity: 97.4%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/19" data-track-dest="link:Figure19 Full size image" aria-label="Full size image figure 19" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec22"><span class="c-article-section__title-number">2.5 </span>Membrane Protein</h3><p>The SARS coronavirus membrane (M) protein is an integral membrane protein that plays an important role in viral assembly [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 54" title="Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG, Siddell SG, Stamou DG, Wilson IA, Kuhn P, Buchmeier MJ (2011) A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11–22" href="/article/10.1007/s10930-020-09901-4#ref-CR54" id="ref-link-section-d447967688e2205">54</a>]. In addition, the SARS coronavirus M protein has been shown to induce apoptosis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 55" title="Tsoi H, Li L, Chen ZS, Lau K-F, Tsui SKW, Chan HYE (2014) The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling. Biochem J 464:439–447" href="/article/10.1007/s10930-020-09901-4#ref-CR55" id="ref-link-section-d447967688e2208">55</a>]. The M protein interacts with the nucleocapsid (N) protein to encapsidate the RNA genome [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 56" title="Siu YL, Teoh KT, Lo J, Chan CM, Kien F, Escriou N, Tsao SW, Nicholls JM, Altmeyer R, Peiris JSM, Bruzzone R, Nal B (2008) The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus re required for efficient assembly, trafficking, and release of virus-like particles. J Virol 82:11318–11330" href="/article/10.1007/s10930-020-09901-4#ref-CR56" id="ref-link-section-d447967688e2211">56</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig20">20</a> shows the amino acid sequence alignment of the two ORF5 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-20" data-title="Fig. 20"><figure><figcaption><b id="Fig20" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 20</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/20" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig20_HTML.png?as=webp"><img aria-describedby="Fig20" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig20_HTML.png" alt="figure 20" loading="lazy" width="685" height="101"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-20-desc"><p>The primary amino acid sequence of the M proteins (ORF5) from SARS CoV (NP_828855.1) and SARS CoV-2 (BCA87364.1). Sequence identity: 90.5%, sequence similarity: 98.2%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/20" data-track-dest="link:Figure20 Full size image" aria-label="Full size image figure 20" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec23"><span class="c-article-section__title-number">2.6 </span>ORF6 Protein</h3><p>The ORF6 protein from SARS coronavirus is an accessory protein that plays an important role in viral pathogenesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 57" title="Kumar P, Gunalan V, Liu B, Chow VTK, Druce J, Birch C, Catton M, Fielding BC, Tan Y-J, Lal SK (2007) The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein. Virology 366:293–303" href="/article/10.1007/s10930-020-09901-4#ref-CR57" id="ref-link-section-d447967688e2242">57</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 58" title="Zhao J, Falcon A, Zhou H, Netlan J, Enjuanes L, Brena PP, Perlman S (2009) Severe acute respiratory syndrome coronavirus protein 6 is required for optimal replication. J Virol 83:2368–2373" href="/article/10.1007/s10930-020-09901-4#ref-CR58" id="ref-link-section-d447967688e2245">58</a>]. Using a yeast two-hybrid system, ORF6 was shown to interact with NSP8, the nonstructural protein related to promoting RNA polymerase activity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 57" title="Kumar P, Gunalan V, Liu B, Chow VTK, Druce J, Birch C, Catton M, Fielding BC, Tan Y-J, Lal SK (2007) The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein. Virology 366:293–303" href="/article/10.1007/s10930-020-09901-4#ref-CR57" id="ref-link-section-d447967688e2248">57</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig21">21</a> shows the amino acid sequence alignment of the two ORF6 proteins from SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-21" data-title="Fig. 21"><figure><figcaption><b id="Fig21" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 21</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/21" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig21_HTML.png?as=webp"><img aria-describedby="Fig21" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig21_HTML.png" alt="figure 21" loading="lazy" width="685" height="30"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-21-desc"><p>The primary amino acid sequence alignment of the ORF6 proteins from SARS CoV (NP_828856.1) and SARS CoV-2 (BCA87365.1). Sequence identity: 68.9%, sequence similarity: 93.4%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/21" data-track-dest="link:Figure21 Full size image" aria-label="Full size image figure 21" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec24"><span class="c-article-section__title-number">2.7 </span>ORF7a Protein</h3><p>ORF7a from SARS coronavirus is an accessory protein that is a type I transmembrane protein and its crystal structure has been determined [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 59" title="Nelson CA, Pekosz A, Lee CA, Diamond MS, Fremont DH (2005) Structure and intracellular targeting of the SARS-coronavirus Orf7a accessory protein. Structure 13:75–85" href="/article/10.1007/s10930-020-09901-4#ref-CR59" id="ref-link-section-d447967688e2279">59</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig22">22</a> shows the amino acid sequence alignment between the two ORF7a proteins of SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-22" data-title="Fig. 22"><figure><figcaption><b id="Fig22" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 22</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/22" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig22_HTML.png?as=webp"><img aria-describedby="Fig22" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig22_HTML.png" alt="figure 22" loading="lazy" width="685" height="66"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-22-desc"><p>The primary amino acid sequence of the ORF7a protein from SARS CoV (NP_828857.1) and SARS CoV-2 (BCA87366.1). Sequence identity: 85.2%, sequence similarity: 95.9%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/22" data-track-dest="link:Figure22 Full size image" aria-label="Full size image figure 22" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec25"><span class="c-article-section__title-number">2.8 </span>ORF7b Protein</h3><p>The ORF7b accessory protein from SARS coronavirus is localized in the Golgi compartment [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 60" title="Schaecher SR, Mackenzie JM, Pekosz A (2007) The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles. J Virol 81:718–731" href="/article/10.1007/s10930-020-09901-4#ref-CR60" id="ref-link-section-d447967688e2310">60</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig23">23</a> shows the sequence alignment between the two ORF7b proteins of SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-23" data-title="Fig. 23"><figure><figcaption><b id="Fig23" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 23</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/23" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig23_HTML.png?as=webp"><img aria-describedby="Fig23" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig23_HTML.png" alt="figure 23" loading="lazy" width="685" height="36"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-23-desc"><p>The primary amino acid sequence of the ORF7b proteins from SARS CoV (NP_849175.1) and SARS CoV-2 (BCB15096.1). Sequence identity: 85.4%, sequence similarity: 97.2%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/23" data-track-dest="link:Figure23 Full size image" aria-label="Full size image figure 23" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec26"><span class="c-article-section__title-number">2.9 </span>ORF8 Protein</h3><p>SARS CoV-2 has a single ORF8 protein while SARS CoV has two ORF8 proteins: ORF8a and ORF8b [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 61" title="Le TM, Wong HH, Tay FPL, Fang S, Keng C-T, Tan YJ, Liu DX (2007) Expression, post-translational modification and biochemical characterization of proteins encoded by subgenomic mRNA8 of the severe acute respiratory syndrome coronavirus. FEBS J 274:4211–4222" href="/article/10.1007/s10930-020-09901-4#ref-CR61" id="ref-link-section-d447967688e2341">61</a>]. In SARS CoV, the ORF8b protein binds to the IRF association domain (IAD) region of interferon regulatory factor 3 (IRF3), which in turn inactivates interferon signaling [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 62" title="Wong HH, Fung TS, Fang S, Huang M, Le MT, Liu DX (2018) Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology 515:165–175" href="/article/10.1007/s10930-020-09901-4#ref-CR62" id="ref-link-section-d447967688e2344">62</a>]. Interestingly, L84S and S62L missense mutations have been reported in various SARS CoV-2 sequences [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Khailany RA, Safdar M, Ozaslan M (2020) Genomic characterisation of a novel SARS-CoV-2. Gene Rep 19:100682" href="/article/10.1007/s10930-020-09901-4#ref-CR5" id="ref-link-section-d447967688e2347">5</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig24">24</a> shows the alignment between the ORF8 protein of SARS CoV-2 with the ORF8a and ORF8b proteins of SARS CoV.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-24" data-title="Fig. 24"><figure><figcaption><b id="Fig24" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 24</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/24" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig24_HTML.png?as=webp"><img aria-describedby="Fig24" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig24_HTML.png" alt="figure 24" loading="lazy" width="685" height="90"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-24-desc"><p>Sequence alignment of ORF8a (NP_849176.1) and ORF8b (NP_849177.1) proteins from SARS CoV (top and middle) with the ORF8 protein (QJA17759.1) from SARS CoV-2 (bottom). Sequence identity and sequence similarity between ORF8a (SARS CoV) and ORF8 (SARS CoV-2): 31.7% and 70.7% in 41 amino acid overlap. Sequence identity and sequence similarity between ORF8b (SARS CoV) and ORF8 (SARS CoV-2): 40.5% and 66.7% in 42 amino acid overlap</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/24" data-track-dest="link:Figure24 Full size image" aria-label="Full size image figure 24" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec27"><span class="c-article-section__title-number">2.10 </span>Nucleocapsid Protein</h3><p>The nucleocapsid (N) protein of coronaviruses is a structural protein that binds directly to viral RNA and providing stability [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 63" title="Grunewald ME, Fehr AR, Athmer J, Perlman S (2018) The coronavirus nucleocapsid protein is ADP-ribosylated. Virology 517:62–68" href="/article/10.1007/s10930-020-09901-4#ref-CR63" id="ref-link-section-d447967688e2379">63</a>]. Furthermore, the N protein of SARS CoV-2 (Fig. <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig24">24</a>) has been found to antagonize antiviral RNAi [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 64" title="Mu J, Xu J, Zhang L, Shu T, Wu D, Huang M, Ren Y, Li X, Geng Q, Xu Y, Qiu Y, Zhou X (2020) SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA interference in cells. Sci China Life Sci 63:10" href="/article/10.1007/s10930-020-09901-4#ref-CR64" id="ref-link-section-d447967688e2385">64</a>]. In another study, the nucleocapsid protein of SARS CoV was found to inhibit the activity of cyclin-cyclin-dependent kinase (cyclin-CDK) complex. Inactivation of the cyclin-CDK complex results in hypophosphorylation of the retinoblastoma protein and in turn inhibits S phase (genome replication) progression in the cell cycle [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 65" title="Surjit M, Liu B, Chow VTK, Lal SK (2006) The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells. J Biol Chem 281:10669–10681" href="/article/10.1007/s10930-020-09901-4#ref-CR65" id="ref-link-section-d447967688e2388">65</a>]. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig25">25</a> shows the amino acid sequence alignment between the two N proteins of SARS CoV and SARS CoV-2.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-25" data-title="Fig. 25"><figure><figcaption><b id="Fig25" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 25</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/25" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig25_HTML.png?as=webp"><img aria-describedby="Fig25" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig25_HTML.png" alt="figure 25" loading="lazy" width="685" height="218"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-25-desc"><p>The primary amino acid sequence of the N protein from SARS CoV (ORF9a, NP_828858.1) and SARS CoV-2 (ORF9, BCA87368.1). Sequence identity: 90.5%, sequence similarity: 97.2%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/25" data-track-dest="link:Figure25 Full size image" aria-label="Full size image figure 25" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><h3 class="c-article__sub-heading" id="Sec28"><span class="c-article-section__title-number">2.11 </span>ORF10 Protein</h3><p>ORF10 protein from SARS CoV-2 is comprised of 38-amino acids and its function is unknown. Interestingly, SARS CoV possesses an ORF9b protein (NP_828859.1), which is not present in SARS CoV-2. Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/article/10.1007/s10930-020-09901-4#Fig26">26</a> shows the sequence alignment between ORF10 of SARS CoV-2 with ORF9b of SARS CoV. SARS CoV-2 does not have an ORF10 protein. A summary of the sequence identities and similarities of the discussed proteins from SARS CoV and SARS CoV-2 is shown in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab3">4</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-26" data-title="Fig. 26"><figure><figcaption><b id="Fig26" class="c-article-section__figure-caption" data-test="figure-caption-text">Fig. 26</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/26" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig26_HTML.png?as=webp"><img aria-describedby="Fig26" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10930-020-09901-4/MediaObjects/10930_2020_9901_Fig26_HTML.png" alt="figure 26" loading="lazy" width="685" height="67"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-26-desc"><p>The primary amino acid sequence alignment of the ORF9b protein from SARS CoV and the ORF10 protein from SARS CoV-2 (Accession number: BCA87369.1). Sequence identity: 28.6%, sequence similarity: 52.4%</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/article/10.1007/s10930-020-09901-4/figures/26" data-track-dest="link:Figure26 Full size image" aria-label="Full size image figure 26" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-3"><figure><figcaption class="c-article-table__figcaption"><b id="Tab3" data-test="table-caption">Table 4 Sequence identity and similarities between SARS CoV-2 proteins and SARS CoV proteins determined through LALIGN (17) (see Supporting Information)</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s10930-020-09901-4/tables/3" aria-label="Full size table 3"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div></div></div></section><section data-title="Overlapping Genes: ORF9b and Two Proteins with Variation Among SARS CoV-2 Sequences: ORF3b and ORF9c"><div class="c-article-section" id="Sec29-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec29"><span class="c-article-section__title-number">3 </span>Overlapping Genes: ORF9b and Two Proteins with Variation Among SARS CoV-2 Sequences: ORF3b and ORF9c</h2><div class="c-article-section__content" id="Sec29-content"><p>Overlapping genes in coronavirus have been previously observed [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 67" title="Rancurel C, Khosravi M, Dunker AK, Romero PR, Karlin D (2009) Overlapping genes produce proteins with unusual sequence properties and offer insight into de novo protein creation. J Virol 83:10719–10736" href="/article/10.1007/s10930-020-09901-4#ref-CR67" id="ref-link-section-d447967688e3285">67</a>]. For example, in SARS CoV, the start and end positions in the nucleotide sequence of the N-protein are 28,120 and 29,388 respectively while the ORF9b gene of SARS CoV starts and ends at positions: 28,130 and 28,426 (within the gene sequence of the N-protein) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 68" title="Shukla A, Hilgenfeld R (2015) Acquisition of new protein domains by coronaviruses: analysis of overlapping genes coding for proteins N and 9b in SARS coronavirus. Virus Genes 50:29–38" href="/article/10.1007/s10930-020-09901-4#ref-CR68" id="ref-link-section-d447967688e3288">68</a>]. Similarly, there is a putative ORF9b protein in SARS CoV-2 located within the gene encoding the N-protein, which does not yet have an accession number [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, Zhang Z (2020) The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol 92:667–674" href="/article/10.1007/s10930-020-09901-4#ref-CR4" id="ref-link-section-d447967688e3291">4</a>].</p><p>In the gene alignment of 2,784 SARS CoV-2 sequences, two variations were recognized in the SARS CoV-2 genome [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 66" title="Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGrego MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang X-P, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O’Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang H-Y, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d’Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, Garcia-Sastre A, Shokat KM, Shoichet BK, Krogan NJ (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 
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" href="/article/10.1007/s10930-020-09901-4#ref-CR66" id="ref-link-section-d447967688e3297">66</a>]. It was recognized that a premature stop codon at position 14 of ORF3b in SARS CoV-2 in 17.6% of isolates (position E14). Furthermore, there were two mutations that gave rise to premature stop codons in ORF9c (at position Q41 in 0.7% of sequences and at position Q44 in 1.4% of the sequences). The observations of these stop codons suggested that these genes for ORF3b and ORF9c may not be bonafide gene sequences in SARS CoV-2. With the putative SARS CoV-2 ORF3b protein, only 12 out of 57 overlapping amino acid residues were identical (21% sequence identity) to the ORF3b protein of SARS CoV [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Chan JF-W, Kok K-H, Zhu Z, Chu H, To KK-W, Yuan S, Yuen K-Y (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 9:221–236" href="/article/10.1007/s10930-020-09901-4#ref-CR3" id="ref-link-section-d447967688e3300">3</a>]. In the above sections, ORF3b and ORF9c for SARS CoV-2 were not included in the above analysis. Another protein lacking an accession number is ORF14 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 69" title="Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, Meng J, Zhu Z, Zhang Z, Wang J, Sheng J, Quan L, Xia Z, Tan W, Cheng G, Jiang T (2020) Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe 27:325–328" href="/article/10.1007/s10930-020-09901-4#ref-CR69" id="ref-link-section-d447967688e3303">69</a>].</p></div></div></section><section data-title="Nontranslated (or Untranslated) Regions of SARS CoV-2 Genome"><div class="c-article-section" id="Sec30-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec30"><span class="c-article-section__title-number">4 </span>Nontranslated (or Untranslated) Regions of SARS CoV-2 Genome</h2><div class="c-article-section__content" id="Sec30-content"><p>Considering the locations of each gene presented in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab1">1</a>, there are regions of the genome that are not translated into proteins, which is related to the non-canonical translational strategy employed by this virus [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 70" title="Firth AE, Brierley I (2012) Non-canonical translation in RNA viruses. J Gen Virol 93:1385–1409" href="/article/10.1007/s10930-020-09901-4#ref-CR70" id="ref-link-section-d447967688e3317">70</a>]. The nucleotide sequences between the genes are the intergenic regions [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 71" title="Hussain S, Pan J, Chen Y, Yang Y, Xu J, Peng Y, Wu Y, Li Z, Zhu Y, Tien P, Guo D (2005) Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J Virol 79:5288–5295" href="/article/10.1007/s10930-020-09901-4#ref-CR71" id="ref-link-section-d447967688e3320">71</a>]. For instance, there is a conserved transctiption regulatory sequence (TRS) – a conserved hexanucleotide sequence: (5′-ACGAAC-3′) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 71" title="Hussain S, Pan J, Chen Y, Yang Y, Xu J, Peng Y, Wu Y, Li Z, Zhu Y, Tien P, Guo D (2005) Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J Virol 79:5288–5295" href="/article/10.1007/s10930-020-09901-4#ref-CR71" id="ref-link-section-d447967688e3323">71</a>] that could be found in between some of the open reading frames (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab4">5</a>, Entries 2, 3, 4, 5, 7, and 9). This particular sequence has previously been identified as the leader-body fusion sites [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 71" title="Hussain S, Pan J, Chen Y, Yang Y, Xu J, Peng Y, Wu Y, Li Z, Zhu Y, Tien P, Guo D (2005) Identification of novel subgenomic RNAs and noncanonical transcription initiation signals of severe acute respiratory syndrome coronavirus. J Virol 79:5288–5295" href="/article/10.1007/s10930-020-09901-4#ref-CR71" id="ref-link-section-d447967688e3330">71</a>]. Furthermore, this sequence is a conserved motif that can be found in subgroup 2b, 2c, and 2d viruses [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 72" title="Quan P-L, Firth C, Street C, Henriquez JA, Petrosov A, Tashumukhamedova A, Hutchison SK, Egholm M, Osinubi MOV, Niezgoda M, Ogunkoya AB, Briese T, Rupprecht CE, Lipkin WI (2010) Identification of a severe acute respiratory syndrome coronavirus-like virus in a leaf-nosed bat in Nigeria. MmBio 1:00208–00210" href="/article/10.1007/s10930-020-09901-4#ref-CR72" id="ref-link-section-d447967688e3333">72</a>]. Another transcriptional regulatory sequence was CUAAAC (e.g. Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab4">5</a>, Entry 1) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 73" title="Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, Hu Y, Tao Z-W, Tian J-H, Pei Y-Y, Yuan M-L, Zhang Y-L, Dai F-H, Liu Y, Wang Q-M, Zheng J-J, Xu L, Holmes EC, Zhang Y-Z (2020) A new coronavirus associated with human respiratory disease in China. Nature 579:265–269" href="/article/10.1007/s10930-020-09901-4#ref-CR73" id="ref-link-section-d447967688e3339">73</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 74" title="Yang D, Leibowitz JL (2015) The structure and functions of coronavirus genomic 3’ and 5’ ends. Virus Res 206:120–133" href="/article/10.1007/s10930-020-09901-4#ref-CR74" id="ref-link-section-d447967688e3342">74</a>].</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-4"><figure><figcaption class="c-article-table__figcaption"><b id="Tab4" data-test="table-caption">Table 5 Nontranslated RNA sequence of SARS CoV-2 (NCBI Reference Sequence: NC_045512.2)</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s10930-020-09901-4/tables/4" aria-label="Full size table 4"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div></div></div></section><section data-title="Exploration of Treatment Options for COVID-19"><div class="c-article-section" id="Sec31-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec31"><span class="c-article-section__title-number">5 </span>Exploration of Treatment Options for COVID-19</h2><div class="c-article-section__content" id="Sec31-content"><p>An intense effort has been put forth to discover potential treatment options for COVID-19, the disease caused by SARS CoV-2 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Jean S-S, Lee P-I, Hsueh P-R (2020) Treatment options for COVID-19: The reality and challenges. J Microbiol. 
 https://doi.org/10.1016/j.jmii.2020.03.034
 
 
" href="#ref-CR75" id="ref-link-section-d447967688e3683">75</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Costanzo M, De Giglio MAR, Roviello GN (2020) SARS-CoV-2: recent reports on antiviral therapies based on lopinavir/ritonavir, darunavir/umifenovir, hydroxychloroquine, remdesivir, favipiravir and other drugs for the treatment of the new coronavirus. Curr Med Chem 27:32297571" href="#ref-CR76" id="ref-link-section-d447967688e3683_1">76</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 77" title="Zeng Q-L, Yu Z-J, Gou J-J, Li G-M, Ma S-H, Zhang G-F, Xu J-H, Lin W-B, Cui G-L, Zhang M-M, Li C, Wang Z-S, Zhang Z-H, Liu Z-S (2020) Effect of convalescent plasma therapy on viral shedding and survival in COVID-19 patients. J Infect Dis. 
 https://doi.org/10.1093/infdis/jiaa228
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR77" id="ref-link-section-d447967688e3686">77</a>]. For instance, the FDA approved drug, ivermectin, is known to inhibit nuclear transport, and has been shown to inhibit the replication of SARS CoV-2 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 78" title="Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (2020) The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 178:104787" href="/article/10.1007/s10930-020-09901-4#ref-CR78" id="ref-link-section-d447967688e3689">78</a>]. Other drugs have been repurposed and tested against COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 79" title="Esposito S, Noviello S, Pagliano P (2020) Update on treatment of COVID-19: ongoing studies between promising and disappointing results. Le Infezioni Med 2:198–211" href="/article/10.1007/s10930-020-09901-4#ref-CR79" id="ref-link-section-d447967688e3692">79</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 80" title="Kupferschmidt K, Cohen J (2020) Race to find COVID-19 treatments accelerates. Science 367:1412–1413" href="/article/10.1007/s10930-020-09901-4#ref-CR80" id="ref-link-section-d447967688e3695">80</a>]. Remdesivir is a potential antiviral drug originally developed to treat ebola [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 81" title="Siegel D, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL (2017) Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f ][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of ebola and emerging viruses. J Med Chem 60:1648–1661" href="/article/10.1007/s10930-020-09901-4#ref-CR81" id="ref-link-section-d447967688e3699">81</a>] and has been used to treat COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 82" title="Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Götte M (2020) Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 
 https://doi.org/10.1074/jbc.RA120.013679
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR82" id="ref-link-section-d447967688e3702">82</a>] by inhibiting viral RNA polymerase activity. Hydroxychloroquine [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 83" title="Meyerowitz EA, Vannier AGL, Friesen MGN, Schoenfeld S, Gelfand JA, Callahan MV, Kim AY, Reeves PM, Poznansky MC (2020) Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J 34(5):6027–6037" href="/article/10.1007/s10930-020-09901-4#ref-CR83" id="ref-link-section-d447967688e3705">83</a>] and chloroquine [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 84" title="Touret F, de Lamballerie X (2020) Of Chloroquine and COVID-19. Antiviral Res 177:104762" href="/article/10.1007/s10930-020-09901-4#ref-CR84" id="ref-link-section-d447967688e3708">84</a>] have been used to potentially treat COVID-19. However, the use of these drugs has been known to result in cardiotoxicity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 85" title="Wong YK, Yang J, He Y (2020) Caution and clarity required in the use of chloroquine for COVID-19. Lancet Rehumatol 2:255" href="/article/10.1007/s10930-020-09901-4#ref-CR85" id="ref-link-section-d447967688e3711">85</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 86" title="Joyce E, Fabre A, Mahon N (2012) Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review. Eur Heart J 2:77–83" href="/article/10.1007/s10930-020-09901-4#ref-CR86" id="ref-link-section-d447967688e3714">86</a>]. In fact, in a recent observational study, it was determined that hydroxychloroquine administration was not associated with a greatly lowered risk of death from COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 87" title="Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, Labella A, Manson D, Kubin C, Barr RG, Sobieszczyk ME, Schluger NW (2020) Obersvational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 
 https://doi.org/10.1056/NEJMoa2012410
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR87" id="ref-link-section-d447967688e3718">87</a>].</p><p>A recent study identified 332 human proteins that interact with SARS CoV-2 proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 66" title="Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGrego MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang X-P, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O’Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang H-Y, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d’Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, Garcia-Sastre A, Shokat KM, Shoichet BK, Krogan NJ (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 
 https://doi.org/10.1038/s41586-020-2286-9
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR66" id="ref-link-section-d447967688e3724">66</a>]. In this report, the predicted SARS CoV-2 proteins (NSPs 1–16 and ORFs) were expressed with 2xstreptavidin affinity tags. These tagged SARS CoV-2 proteins were expressed in human embryonic kidney (HEK)293T/17 cells and isolated the viral protein-(human protein) interactions using affinity purification-mass spectrometry. A total 332 protein–protein interactions (PPIs between SARS CoV-2 proteins and human proteins) were identified. Of these PPIs, 66 of them are targetable by compounds. Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s10930-020-09901-4#Tab5">6</a> shows a set of compounds that target the identified PPIs based on chemoinformatics (entries 1–28) or expertise knowledge (entries 29–44). From the subset of potential antiviral compounds that were tested, two classes of compounds were found to be effective against viral pathogenesis: [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Li X, Zai J, Wang X, Li Y (2020) Potential of large “first generation” human-to-human transmission of 2019-nCoV. J Med Virol 92:448–454" href="/article/10.1007/s10930-020-09901-4#ref-CR1" id="ref-link-section-d447967688e3730">1</a>] protein translation inhibitors (i.e. zotatifin, ternatin-4, and PS3061), and [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Gralinski LE, Menachery VD (2020) Return of the Coronavirus: 2019-nCoV. Viruses 12:135" href="/article/10.1007/s10930-020-09901-4#ref-CR2" id="ref-link-section-d447967688e3733">2</a>] Sigma1 and Sigma2 receptor ligands (i.e. approved drugs: clemastine, cloperastine, and progesterone and PB28, which was ~ 20 times more potent than hydroxychloroquine with an IC<sub>90</sub> of 280 nM in the viral titer assay is undergoing pre-clinical trials for anti-cancer [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 88" title="Pati ML, Hornick JR, Niso M, Berardi F, Spitzer D, Abate C, Hawkins W (2017) Sigma-2 receptor agonist derivatives of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer. BMC Cancer 17:51" href="/article/10.1007/s10930-020-09901-4#ref-CR88" id="ref-link-section-d447967688e3739">88</a>] activity).</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-5"><figure><figcaption class="c-article-table__figcaption"><b id="Tab5" data-test="table-caption">Table 6 Drugs that potentially target (modulate) proteins that interact with SARS CoV-2 proteins as described in reference [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 66" title="Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGrego MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang X-P, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O’Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang H-Y, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d’Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, Garcia-Sastre A, Shokat KM, Shoichet BK, Krogan NJ (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 
 https://doi.org/10.1038/s41586-020-2286-9
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR66" id="ref-link-section-d447967688e3752">66</a>]</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s10930-020-09901-4/tables/5" aria-label="Full size table 5"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Moreover, in another collaborative study, a library of 12,000 FDA-approved or clinical-stage drugs were tested against SARS CoV-2 infection in Vero-E6 (African green monkey kidney) cells [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 89" title="Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Burgstaller-Muehlbacher S, Pache L, De Jesus PP, Hull MV, Chang M, Chan JF-W, Cao J, Poon VK-M, Herbert K, Nguyen T-T, Pu Y, Nguyen C, Rubanov A, Martinez-Sobrido L, Liu W-C, Miorin L, White KM, Johnson JR, Benner C, Sun R, Schultz PG, Su A, Garcia-Sastre A, Chatterjee AK, Yuen K-Y, Chanda SK (2020) A Large-scale drug repositioning survey for SARS-CoV-2 antivirals. bioRxiv. 
 https://doi.org/10.1101/2020.04.16.044016
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR89" id="ref-link-section-d447967688e4744">89</a>]. Some effective compounds identified in the screen were: PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors (MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334), and MLN-3897 (a CCR1 antagonist).</p><p>Traditional Chinese Medicine (TCM) has also been employed in China to treat COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 90" title="Xu J, Zhang Y (2020) Traditional Chinese Medicine treatment of COVID-19. Complement Ther Clin Pract 39:101165" href="/article/10.1007/s10930-020-09901-4#ref-CR90" id="ref-link-section-d447967688e4750">90</a>]. However, due to potential toxic components present in TCM remedies, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 91" title="Chen C-H, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu X-R, Pu Y-S, Grollman AP (2012) Aristolochic acid-associated urothelial cancer in Taiwan. Proc Natl Acad Sci USA 109:8241–8246" href="/article/10.1007/s10930-020-09901-4#ref-CR91" id="ref-link-section-d447967688e4753">91</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 92" title="Duan L, Guo L, Wang L, Yin Q, Zhang C-M et al (2018) Application of metabolomics in toxicity evaluation of traditional Chinese medicines. Chin Med 13:60" href="/article/10.1007/s10930-020-09901-4#ref-CR92" id="ref-link-section-d447967688e4756">92</a>] the use of this strategy should be handled with caution [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 93" title="Lv W, Piao J-H, Jiang J-G (2012) Typical toxic components in traditional Chinese medicine. Expert Opin Drug Saf 11:985–1002" href="/article/10.1007/s10930-020-09901-4#ref-CR93" id="ref-link-section-d447967688e4759">93</a>]. Ironically, it has been suggested that TCM could have potentially been the cause of COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 94" title="Wassenaar TM, Zou Y (2020) 2019_nCoV/SARS-CoV-2: rapid classification of betacorona viruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses. Lett Appl Microbiol 70:342–348" href="/article/10.1007/s10930-020-09901-4#ref-CR94" id="ref-link-section-d447967688e4762">94</a>].</p><p>In addition to small molecules, vaccines are also currently being developed against SARS CoV-2, [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 95" title="Lurie N, Saville M, Hatchett R, Halton J (2020) Developing Covid-19 vaccines at pandemic speed. N Engl J Med. 
 https://doi.org/10.1056/NEJMp2005630
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR95" id="ref-link-section-d447967688e4769">95</a>] and convalescent plasma transfusions have been used to treat COVID-19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 96" title="Brown BL, McCullough J (2020) Treatment for emerging viruses: convalescent plasma and COVID-19. Transfus Apher Sci. 
 https://doi.org/10.1016/j.transci.2020.102790
 
 
" href="/article/10.1007/s10930-020-09901-4#ref-CR96" id="ref-link-section-d447967688e4772">96</a>]. Nevertheless, more research is needed to develop effective treatments against SARS CoV-2 especially in the context of future outbreaks [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 97" title="Xu S, Li Y (2020) Beware of the second wave of COVID-19. Lancet 395:1321–1322" href="/article/10.1007/s10930-020-09901-4#ref-CR97" id="ref-link-section-d447967688e4775">97</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 98" title="Leung K, Wu JT, Liu D, Leung GM (2020) First-wave COVID-19 transmissibility and severity in China outside Hubei after control measures, and second-wave scenario planning: a modelling impact assessment. Lancet 395:1382–1393" href="/article/10.1007/s10930-020-09901-4#ref-CR98" id="ref-link-section-d447967688e4778">98</a>].</p></div></div></section><section data-title="Conclusion"><div class="c-article-section" id="Sec32-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec32"><span class="c-article-section__title-number">6 </span>Conclusion</h2><div class="c-article-section__content" id="Sec32-content"><p>Although there is some variation in sequence in the proteins, many of the proteins found in SARS CoV-2 (NC_045512.2) are also found in SARS CoV (AY515512.1 or NC_004718.3) with 77.1% of the protein sequences shared in their proteomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 99" title="Ceraolo C, Giorgi FM (2020) Genomic variance of the 2019-nCoV coronavirus. J Med Virol 92:522–528" href="/article/10.1007/s10930-020-09901-4#ref-CR99" id="ref-link-section-d447967688e4790">99</a>]. Thus, previous research on related coronavirus proteins enable a better understanding of how we can approach to understand the current coronavirus (SARS CoV-2) that caused the current global pandemic (COVID-19). The general structures of most of the proteins from SARS CoV-2 can be visualized from homology models [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 100" title="

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Yoshimoto, PhD holds a Voelcker Fund Young Investigator Award from the MAX AND MINNIE TOMERLIN VOELCKER FUND.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Chemistry, The University of Texas at San Antonio (UTSA), San Antonio, TX, 78249-0698, USA</p><p class="c-article-author-affiliation__authors-list">Francis K. Yoshimoto</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Francis_K_-Yoshimoto-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Francis K. 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The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. <i>Protein J</i> <b>39</b>, 198–216 (2020). https://doi.org/10.1007/s10930-020-09901-4</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s10930-020-09901-4?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time 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