8doy
From Proteopedia
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==Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-198== | ==Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-198== | ||
| - | <StructureSection load='8doy' size='340' side='right'caption='[[8doy]]' scene=''> | + | <StructureSection load='8doy' size='340' side='right'caption='[[8doy]], [[Resolution|resolution]] 1.59Å' 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=8DOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DOY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[8doy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DOY FirstGlance]. <br> |
| - | </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=8doy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8doy OCA], [https://pdbe.org/8doy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8doy RCSB], [https://www.ebi.ac.uk/pdbsum/8doy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8doy ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=T1X:7-fluoranyl-~{N}-[(2~{S})-1-[[(1~{S},2~{S})-1-(4-fluoranyl-1,3-benzothiazol-2-yl)-1-oxidanyl-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]-4-methoxy-1~{H}-indole-2-carboxamide'>T1X</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=8doy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8doy OCA], [https://pdbe.org/8doy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8doy RCSB], [https://www.ebi.ac.uk/pdbsum/8doy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8doy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Potent and biostable inhibitors of the main protease (M(pro)) of SARS-CoV-2 were designed and synthesized based on an active hit compound 5h (2). Our strategy was based not only on the introduction of fluorine atoms into the inhibitor molecule for an increase of binding affinity for the pocket of M(pro) and cell membrane permeability but also on the replacement of the digestible amide bond by a surrogate structure to increase the biostability of the compounds. Compound 3 is highly potent and blocks SARS-CoV-2 infection in vitro without a viral breakthrough. The derivatives, which contain a thioamide surrogate in the P2-P1 amide bond of these compounds (2 and 3), showed remarkably preferable pharmacokinetics in mice compared with the corresponding parent compounds. These data show that compounds 3 and its biostable derivative 4 are potential drugs for treating COVID-19 and that replacement of the digestible amide bond by its thioamide surrogate structure is an effective method. | ||
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| + | Potent and biostable inhibitors of the main protease of SARS-CoV-2.,Tsuji K, Ishii T, Kobayakawa T, Higashi-Kuwata N, Azuma C, Nakayama M, Onishi T, Nakano H, Wada N, Hori M, Shinohara K, Miura Y, Kawada T, Hayashi H, Hattori SI, Bulut H, Das D, Takamune N, Kishimoto N, Saruwatari J, Okamura T, Nakano K, Misumi S, Mitsuya H, Tamamura H iScience. 2022 Nov 18;25(11):105365. doi: 10.1016/j.isci.2022.105365. Epub 2022 , Nov 1. PMID:36338434<ref>PMID:36338434</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8doy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Bulut H]] | [[Category: Bulut H]] | ||
[[Category: Das D]] | [[Category: Das D]] | ||
Current revision
Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-198
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