6vh0: Difference between revisions
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==1.95 A resolution structure of MERS 3CL protease in complex with inhibitor 6g== | ==1.95 A resolution structure of MERS 3CL protease in complex with inhibitor 6g== | ||
<StructureSection load='6vh0' size='340' side='right'caption='[[6vh0]]' scene=''> | <StructureSection load='6vh0' size='340' side='right'caption='[[6vh0]], [[Resolution|resolution]] 1.95Å' 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=6VH0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VH0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6vh0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VH0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VH0 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vh0 OCA], [http://pdbe.org/6vh0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vh0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vh0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vh0 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QZD:N~2~-{[(5-ethyl-1,3-dioxan-5-yl)oxy]carbonyl}-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-leucinamide'>QZD</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">orf1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1335626 MERS])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vh0 OCA], [http://pdbe.org/6vh0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vh0 RCSB], [http://www.ebi.ac.uk/pdbsum/6vh0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vh0 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pathogenic coronaviruses are a major threat to global public health, as exemplified by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound one day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses. | |||
3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.,Rathnayake AD, Zheng J, Kim Y, Perera KD, Mackin S, Meyerholz DK, Kashipathy MM, Battaile KP, Lovell S, Perlman S, Groutas WC, Chang KO Sci Transl Med. 2020 Aug 3. pii: scitranslmed.abc5332. doi:, 10.1126/scitranslmed.abc5332. PMID:32747425<ref>PMID:32747425</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6vh0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Battaile | [[Category: Mers]] | ||
[[Category: Chang | [[Category: Battaile, K P]] | ||
[[Category: Groutas | [[Category: Chang, K O]] | ||
[[Category: Kashipathy | [[Category: Groutas, W C]] | ||
[[Category: Kim Y]] | [[Category: Kashipathy, M M]] | ||
[[Category: Lovell S]] | [[Category: Kim, Y]] | ||
[[Category: Nguyen | [[Category: Lovell, S]] | ||
[[Category: Rathnayake | [[Category: Nguyen, H N]] | ||
[[Category: Zheng J]] | [[Category: Rathnayake, A D]] | ||
[[Category: Zheng, J]] | |||
[[Category: Hydrolase]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Mers 3cl protease inhhibitor]] | |||
[[Category: Protease]] | |||
Revision as of 09:36, 19 August 2020
1.95 A resolution structure of MERS 3CL protease in complex with inhibitor 6g1.95 A resolution structure of MERS 3CL protease in complex with inhibitor 6g
Structural highlights
Publication Abstract from PubMedPathogenic coronaviruses are a major threat to global public health, as exemplified by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound one day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.,Rathnayake AD, Zheng J, Kim Y, Perera KD, Mackin S, Meyerholz DK, Kashipathy MM, Battaile KP, Lovell S, Perlman S, Groutas WC, Chang KO Sci Transl Med. 2020 Aug 3. pii: scitranslmed.abc5332. doi:, 10.1126/scitranslmed.abc5332. PMID:32747425[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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