7wo2
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==SARS-CoV-2 3CLPro Peptidomimetic Inhibitor TPM5== | |
| + | <StructureSection load='7wo2' size='340' side='right'caption='[[7wo2]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7wo2]] is a 1 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=7WO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WO2 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]] 1.96Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40I:~{N}-[(2~{S})-3-methyl-1-[[(2~{S})-4-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepiperidin-3-yl]propan-2-yl]amino]pentan-2-yl]amino]-1-oxidanylidene-butan-2-yl]furan-2-carboxamide'>40I</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=7wo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wo2 OCA], [https://pdbe.org/7wo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wo2 RCSB], [https://www.ebi.ac.uk/pdbsum/7wo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wo2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | As the etiological agent for the coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges the ongoing efforts of vaccine development and drug design. Due to the accumulating cases of breakthrough infections, there are urgent needs for broad-spectrum antiviral medicines. Here, we designed and examined five new tetrapeptidomimetic anti-SARS-CoV-2 inhibitors targeting the 3C-Like protease (3CL(Pro)), which is highly conserved among coronaviruses and essential for viral replications. We significantly improved the efficacy of a ketoamide lead compound based on high-resolution co-crystal structures, all-atom simulations, and binding energy calculations. The inhibitors successfully engaged the catalytic dyad histidine residue (H41) of 3CLPro as designed, and they exhibited nanomolar inhibitory capacity as well as mitigated the viral loads of SARS-CoV-2 in cellular assays. As a widely applicable design principle, our results revealed that the potencies of 3CL(Pro)-specific drug candidates were determined by the interplay between 3CL(Pro) H41 residue and the peptidomimetic inhibitors. | ||
| - | + | Discovery of SARS-CoV-2 3CL(Pro) Peptidomimetic Inhibitors through the Catalytic Dyad Histidine-Specific Protein-Ligand Interactions.,Wang Y, Xu B, Ma S, Wang H, Shang L, Zhu C, Ye S Int J Mol Sci. 2022 Feb 21;23(4):2392. doi: 10.3390/ijms23042392. PMID:35216507<ref>PMID:35216507</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Wang | + | <div class="pdbe-citations 7wo2" style="background-color:#fffaf0;"></div> |
| - | [[Category: Ye | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
| + | [[Category: Wang Y]] | ||
| + | [[Category: Ye S]] | ||
Current revision
SARS-CoV-2 3CLPro Peptidomimetic Inhibitor TPM5
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