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<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <title>Welcome to the DeRisi Lab</title> <link href="derisilab.css" rel="stylesheet" type="text/css"> </head> <body> <table border="0" cellspacing="0" cellpadding="0" align="center" bgcolor="#FFFFFF"> <tr><td width="800"> <table border="0" cellspacing="0" cellpadding="0" align="center" > <tr> <td id="menu_bar_top" colspan="2" class="menubar" align="middle" bgcolor="#000000"> <center> <a href='http://www.ncbi.nlm.nih.gov/BLAST/'>BLAST</a> :: <a href='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed'>PubMed</a> :: <a href='http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi'>Entrez</a> :: <a href='http://www.plasmodb.org'>PlasmoDB</a> :: <a href='http://www.yeastgenome.org/'>SGD</a> :: <a href='http://czbiohub.org'>CZ Biohub</a> :: <a href='http://www.plos.org'>PLoS</a> :: <a href='http://directory.ucsf.edu/people_search.jsp'>Directory</a> :: <a href='http://www.ucsf.edu'>UCSF</a> </center> </td> </tr> <tr> <td colspan="2" bgcolor="#000000"> <img src='images/pentamers_3.jpg' width='800' height='160'> </td> </tr> <tr> <td id="menu_bar_main" class="menubar" align='middle' colspan='2' bgcolor="#000000"> <center> <a href='index.php'>News</a> :: <a href='index.php?page=research'>Research</a> :: <a href='index.php?page=publications'>Publications</a> :: <a href='index.php?page=data'>Data</a> :: <a href='index.php?page=software'>Software</a> :: <a href='index.php?page=3D'>3D Printables</a> :: <a href='index.php?page=people'>People</a> :: <a href='index.php?page=contact'>Contact</a> </center> </td> </tr> <tr> <td class='hlink' valign='top' colspan='2'><br> <a name='anchor-364'></a> <table border='0' cellspacing='0' cellpadding='0'> <tr> <td width='6' height='20' id='left_rbar'></td> <td width='100' height='20' valign='middle' id='middle_rbar' class='menubar'>2023-03-02 </td> <td width='488' height='20' valign='middle' id='middle_rbar' class='menubar'> </td> <td width='200' height='20' valign='middle' align='right' id='middle_rbar' class='menubar'> <a href='pdfs/Rosenberg1.pdf' target='_blank'>[ PDF ]</a></td> <td width='6' height='20' id='right_rbar'></td> </tr></table> <table border='0' cellspacing='0' cellpadding='0'> <tr><td><div class='longleftbox'><img src='webicons/rosen1.jpg' class='iconbox'> <b>Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps</b><br>Soumya G Remesh, Gregory E Merz, Axel F Brilot, Un Seng Chio, Alexandrea N Rizo, Thomas H Pospiech Jr, Irene Lui, Mathew T Laurie, Jeff Glasgow, Chau Q Le, Yun Zhang, Devan Diwanji, Evelyn Hernandez, Jocelyne Lopez, Hevatib Mehmood, Komal Ishwar Pawar, Sergei Pourmal, Amber M Smith, Fengbo Zhou; QCRG Structural Biology Consortium; Joseph DeRisi, Tanja Kortemme, Oren S Rosenberg, Anum Glasgow, Kevin K Leung, James A Wells, Kliment A Verba<br><br><i>Science Direct, 2023</i><br><br><b><i>Abstract:</i></b> The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor-binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-RBD and prevent viral entry into host cells (receptor traps). Here we determine cryo-EM structures of our receptor traps in complex with stabilized Spike ectodomain. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high-affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high-affinity (0.53-4.2 nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron and Delta pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus.<br class='clearfix' /></div></td></tr></table><br></td> </tr> </table> </body> </html>