View source for 7rbz


==X-ray Structure of SARS-CoV-2 main protease covalently modified by compound GRL-017-20==
<StructureSection load='7rbz' size='340' side='right'caption='[[7rbz]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RBZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4IJ:5-chloropyridin-3-yl+2,3-dihydro-1H-indole-4-carboxylate'>4IJ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rbz OCA], [https://pdbe.org/7rbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rbz RCSB], [https://www.ebi.ac.uk/pdbsum/7rbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rbz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Here, we report the synthesis, structure-activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as a potent class of SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound 1 exhibited a SARS-CoV-2 3CLpro inhibitory IC50 value of 250 nM and an antiviral EC50 value of 2.8 muM in VeroE6 cells. Remdesivir, an RNA-dependent RNA polymerase inhibitor, showed an antiviral EC50 value of 1.2 muM in the same assay. Compound 1 showed comparable antiviral activity with remdesivir in immunocytochemistry assays. Compound 7d with an N-allyl derivative showed the most potent enzyme inhibitory IC50 value of 73 nM. To obtain molecular insight into the binding properties of these molecules, X-ray crystal structures of compounds 2, 7b, and 9d-bound to SARS-CoV 3CLpro were determined, and their binding properties were compared.

Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure-Activity Relationship, and X-ray Structural Studies.,Ghosh AK, Raghavaiah J, Shahabi D, Yadav M, Anson BJ, Lendy EK, Hattori SI, Higashi-Kuwata N, Mitsuya H, Mesecar AD J Med Chem. 2021 Sep 16. doi: 10.1021/acs.jmedchem.1c01214. PMID:34528437<ref>PMID:34528437</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rbz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Anson BA]]
[[Category: Ghosh AK]]
[[Category: Mesecar AD]]