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==Structure of the SARS-CoV-2 main protease in complex with inhibitor MPI6==
<StructureSection load='7jq3' size='340' side='right'caption='[[7jq3]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JQ3 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=VHP:N-[(benzyloxy)carbonyl]-O-tert-butyl-L-threonyl-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide'>VHP</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=7jq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jq3 OCA], [https://pdbe.org/7jq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jq3 RCSB], [https://www.ebi.ac.uk/pdbsum/7jq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jq3 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M(Pro) ) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1M(Pro) ), we have designed and synthesized a series of SC2M(Pro) inhibitors that contain beta-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2M(Pro) active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2M(Pro) bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 muM and A549/ACE2 cells at 0.16-0.31 muM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2M(Pro) inhibitors with ultra-high antiviral potency.

A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors*.,Yang KS, Ma XR, Ma Y, Alugubelli YR, Scott DA, Vatansever EC, Drelich AK, Sankaran B, Geng ZZ, Blankenship LR, Ward HE, Sheng YJ, Hsu JC, Kratch KC, Zhao B, Hayatshahi HS, Liu J, Li P, Fierke CA, Tseng CK, Xu S, Liu WR ChemMedChem. 2020 Dec 7. doi: 10.1002/cmdc.202000924. PMID:33283984<ref>PMID:33283984</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7jq3" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Liu W]]
[[Category: Yang K]]