8hht: Difference between revisions

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-'''Unreleased structure'''
-The entry 8hht is ON HOLD  until Paper Publication
+==Crystal structure of the SARS-CoV-2 main protease in complex with Hit-1==
+<StructureSection load='8hht' size='340' side='right'caption='[[8hht]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8hht]] 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=8HHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HHT FirstGlance]. <br>
+</td></tr><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=LV0:~{N}-[(2~{R},3~{S})-3-oxidanyl-4-oxidanylidene-1-phenyl-4-(1,3-thiazol-2-ylmethylamino)butan-2-yl]benzamide'>LV0</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=8hht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hht OCA], [https://pdbe.org/8hht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hht RCSB], [https://www.ebi.ac.uk/pdbsum/8hht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hht ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health. Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals either show limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these drugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a new generation antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (M(pro)). This compound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, but also other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2 mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology. Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstanding safety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance M(pro) mutations. Collectively, this investigation provides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.
-Authors: Zeng, R., Xie, L.W., Huang, C., Wang, K., Liu, Y.Z., Yang, S.Y., Lei, J.
+A new generation M(pro) inhibitor with potent activity against SARS-CoV-2 Omicron variants.,Huang C, Shuai H, Qiao J, Hou Y, Zeng R, Xia A, Xie L, Fang Z, Li Y, Yoon C, Huang Q, Hu B, You J, Quan B, Zhao X, Guo N, Zhang S, Ma R, Zhang J, Wang Y, Yang R, Zhang S, Nan J, Xu H, Wang F, Lei J, Chu H, Yang S Signal Transduct Target Ther. 2023 Mar 16;8(1):128. doi: , 10.1038/s41392-023-01392-w. PMID:36928316<ref>PMID:36928316</ref>
-Description: Crystal structure of the SARS-CoV-2 main protease in complex with Hit-1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Liu, Y.Z]]
+<div class="pdbe-citations 8hht" style="background-color:#fffaf0;"></div>
-[[Category: Xie, L.W]]
+== References ==
-[[Category: Yang, S.Y]]
+<references/>
-[[Category: Zeng, R]]
+__TOC__
-[[Category: Huang, C]]
+</StructureSection>
-[[Category: Wang, K]]
+[[Category: Large Structures]]
-[[Category: Lei, J]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Huang C]]
+[[Category: Lei J]]
+[[Category: Liu YZ]]
+[[Category: Wang K]]
+[[Category: Xie LW]]
+[[Category: Yang SY]]
+[[Category: Zeng R]]