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8i4s

From Proteopedia

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Current revision

the complex structure of SARS-CoV-2 Mpro with D8

Structural highlights

8i4s is a 1 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A8B1JQ63_SARS2

Publication Abstract from PubMed

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (M(pro)) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 M(pro) inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior inhibitory activity against SARS-CoV-2 M(pro) relative to baicalein (IC(50) = 0.085 +/- 0.006 and 0.966 +/- 0.065 muM, respectively), as well as improved physicochemical and drug metabolism and pharmacokinetics (DMPK) properties. In addition, C7 inhibits viral replication in SARS-CoV-2-infected Vero E6 cells more effectively than baicalein (EC(50) = 1.10 +/- 0.12 and 5.15 +/- 1.64 muM, respectively) with low cytotoxicity (CC(50) ï¼ 50 muM). An X-ray co-crystal structure reveals a non-covalent mechanism of action, and a noncanonical binding mode not observed by baicalein. These results suggest that C7 represents a promising lead for development of more effective SARS-CoV-2 M(pro) inhibitors and anti-COVID-19 drugs.

Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M(pro)).,Zhang K, Wang T, Li M, Liu M, Tang H, Wang L, Ye K, Yang J, Jiang S, Xiao Y, Xie Y, Lu M, Zhang X Eur J Med Chem. 2023 Sep 5;257:115487. doi: 10.1016/j.ejmech.2023.115487. Epub , 2023 May 24. PMID:37257212^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang K, Wang T, Li M, Liu M, Tang H, Wang L, Ye K, Yang J, Jiang S, Xiao Y, Xie Y, Lu M, Zhang X. Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M(pro)). Eur J Med Chem. 2023 Sep 5;257:115487. PMID:37257212 doi:10.1016/j.ejmech.2023.115487

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8i4s"

Categories: Large Structures | Severe acute respiratory syndrome coronavirus 2 | Lu M

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8i4s is ON HOLD  until Paper Publication
+==the complex structure of SARS-CoV-2 Mpro with D8==
+<StructureSection load='8i4s' size='340' side='right'caption='[[8i4s]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8i4s]] 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=8I4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I4S 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OU3:3-(4-fluoranyl-3-methyl-phenyl)-2-(2-methylpropyl)-5,6,7-tris(oxidanyl)quinazolin-4-one'>OU3</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=8i4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i4s OCA], [https://pdbe.org/8i4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i4s RCSB], [https://www.ebi.ac.uk/pdbsum/8i4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i4s ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A8B1JQ63_SARS2 A0A8B1JQ63_SARS2]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a great threat to public health while various vaccines are available worldwide. Main protease (M(pro)) has been validated as an effective anti-COVID-19 drug target. Using medicinal chemistry and rational drug design strategies, we identified a quinazolin-4-one series of nonpeptidic, noncovalent SARS-CoV-2 M(pro) inhibitors based on baicalein, 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one. In particular, compound C7 exhibits superior inhibitory activity against SARS-CoV-2 M(pro) relative to baicalein (IC(50) = 0.085 +/- 0.006 and 0.966 +/- 0.065 muM, respectively), as well as improved physicochemical and drug metabolism and pharmacokinetics (DMPK) properties. In addition, C7 inhibits viral replication in SARS-CoV-2-infected Vero E6 cells more effectively than baicalein (EC(50) = 1.10 +/- 0.12 and 5.15 +/- 1.64 muM, respectively) with low cytotoxicity (CC(50) ï¼ 50 muM). An X-ray co-crystal structure reveals a non-covalent mechanism of action, and a noncanonical binding mode not observed by baicalein. These results suggest that C7 represents a promising lead for development of more effective SARS-CoV-2 M(pro) inhibitors and anti-COVID-19 drugs.
-Authors:
+Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M(pro)).,Zhang K, Wang T, Li M, Liu M, Tang H, Wang L, Ye K, Yang J, Jiang S, Xiao Y, Xie Y, Lu M, Zhang X Eur J Med Chem. 2023 Sep 5;257:115487. doi: 10.1016/j.ejmech.2023.115487. Epub , 2023 May 24. PMID:37257212<ref>PMID:37257212</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8i4s" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Lu M]]

8i4s

From Proteopedia

Current revision

the complex structure of SARS-CoV-2 Mpro with D8

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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