Open AccessOridonin Inhibits SARS‐CoV‐2 by Targeting Its 3C‐Like Protease
Author(s) -
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
Publication year - 2022
Publication title -
small science
Language(s) - English
Resource type - Journals
ISSN - 2688-4046
DOI - 10.1002/smsc.202100124
Subject(s) - chemistry , coronavirus , protease , covalent bond , enzyme , viral replication , virology , pharmacology , covid-19 , biochemistry , virus , biology , medicine , disease , organic chemistry , pathology , infectious disease (medical specialty)
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 CS 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.