Issue 42, 2021

Allosteric inhibition of SARS-CoV-2 3CL protease by colloidal bismuth subcitrate

Abstract

The SARS-CoV-2 3-chymotrypsin-like protease (3CLpro or Mpro) is a key cysteine protease for viral replication and transcription, making it an attractive target for antiviral therapies to combat the COVID-19 disease. Here, we demonstrate that bismuth drug colloidal bismuth subcitrate (CBS) is a potent inhibitor for 3CLpro in vitro and in cellulo. Rather than targeting the cysteine residue at the catalytic site, CBS binds to an allosteric site and results in dissociation of the 3CLpro dimer and proteolytic dysfunction. Our work provides direct evidence that CBS is an allosteric inhibitor of SARS-CoV-2 3CLpro.

Graphical abstract: Allosteric inhibition of SARS-CoV-2 3CL protease by colloidal bismuth subcitrate

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jun 2021
Accepted
24 Sep 2021
First published
24 Sep 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 14098-14102

Allosteric inhibition of SARS-CoV-2 3CL protease by colloidal bismuth subcitrate

X. Tao, L. Zhang, L. Du, R. Liao, H. Cai, K. Lu, Z. Zhao, Y. Xie, P. Wang, J. Pan, Y. Zhang, G. Li, J. Dai, Z. Mao and W. Xia, Chem. Sci., 2021, 12, 14098 DOI: 10.1039/D1SC03526F

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