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Oridonin Inhibits SARS‐CoV‐2 by Targeting Its 3C‐Like Protease.

Authors :
Zhong, Baisen
Peng, Weiyu
Du, Shan
Chen, Bingyi
Feng, Yajuan
Hu, Xinfeng
Lai, Qi
Liu, Shujie
Zhou, Zhong-Wei
Fang, Pengfei
Wu, Yan
Gao, Feng
Zhou, Huihao
Sun, Litao
Source :
Small Science; Jun2022, Vol. 2 Issue 6, p1-10, 10p
Publication Year :
2022

Abstract

The current COVID‐19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is an enormous threat to public health. The SARS‐CoV‐2 3C‐like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (–)‐Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS‐CoV‐2 3CLpro. Further, blocking SARS‐CoV‐2 infectivity by Oridonin is confirmed in cell‐based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a CS covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID‐19. [ABSTRACT FROM AUTHOR]

Details

Language :
English
Volume :
2
Issue :
6
Database :
Complementary Index
Journal :
Small Science
Publication Type :
Academic Journal
Accession number :
157397979
Full Text :
https://doi.org/10.1002/smsc.202100124