7aeh

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==SARS-CoV-2 main protease in a covalent complex with a pyridine derivative of ABT-957, compound 1==
==SARS-CoV-2 main protease in a covalent complex with a pyridine derivative of ABT-957, compound 1==
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<StructureSection load='7aeh' size='340' side='right'caption='[[7aeh]]' scene=''>
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<StructureSection load='7aeh' size='340' side='right'caption='[[7aeh]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEH FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AEH FirstGlance]. <br>
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</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=7aeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeh OCA], [https://pdbe.org/7aeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeh RCSB], [https://www.ebi.ac.uk/pdbsum/7aeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeh ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=R8H:(2~{R})-5-oxidanylidene-~{N}-[(2~{R},3~{S})-3-oxidanyl-4-oxidanylidene-1-phenyl-4-(pyridin-2-ylmethylamino)butan-2-yl]-1-(phenylmethyl)pyrrolidine-2-carboxamide'>R8H</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aeh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aeh OCA], [https://pdbe.org/7aeh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aeh RCSB], [https://www.ebi.ac.uk/pdbsum/7aeh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aeh ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak. Protecting against future outbreaks requires the identification of targets that are conserved between coronavirus strains and amenable to drug discovery. Two such targets are the main protease (M(pro)) and the papain-like protease (PL(pro)) which are essential for the coronavirus replication cycle. We describe the discovery of two non-antiviral therapeutic agents, the caspase-1 inhibitor SDZ 224015 and Tarloxotinib that target M(pro) and PL(pro), respectively. These were identified through extensive experimental screens of the drug repurposing ReFRAME library of 12,000 therapeutic agents. The caspase-1 inhibitor SDZ 224015, was found to be a potent irreversible inhibitor of M(pro) (IC50 30 nM) while Tarloxotinib, a clinical stage epidermal growth factor receptor inhibitor, is a sub micromolar inhibitor of PL(pro) (IC50 300 nM, Ki 200 nM) and is the first reported PL(pro) inhibitor with drug-like properties. SDZ 224015 and Tarloxotinib have both undergone safety evaluation in humans and hence are candidates for COVID-19 clinical evaluation.
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Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19.,Redhead MA, Owen CD, Brewitz L, Collette AH, Lukacik P, Strain-Damerell C, Robinson SW, Collins PM, Schafer P, Swindells M, Radoux CJ, Hopkins IN, Fearon D, Douangamath A, von Delft F, Malla TR, Vangeel L, Vercruysse T, Thibaut J, Leyssen P, Nguyen TT, Hull M, Tumber A, Hallett DJ, Schofield CJ, Stuart DI, Hopkins AL, Walsh MA Sci Rep. 2021 Jun 24;11(1):13208. doi: 10.1038/s41598-021-92416-4. PMID:34168183<ref>PMID:34168183</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7aeh" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

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SARS-CoV-2 main protease in a covalent complex with a pyridine derivative of ABT-957, compound 1

PDB ID 7aeh

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