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

被引:30
|
作者
Zhong, Baisen [1 ]
Peng, Weiyu [2 ]
Du, Shan [1 ]
Chen, Bingyi [3 ]
Feng, Yajuan [1 ]
Hu, Xinfeng [1 ]
Lai, Qi [1 ]
Liu, Shujie [4 ]
Zhou, Zhong-Wei [4 ]
Fang, Pengfei [5 ]
Wu, Yan [6 ]
Gao, Feng [7 ]
Zhou, Huihao [3 ]
Sun, Litao [1 ]
机构
[1] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen Campus, Shenzhen 518107, Peoples R China
[2] Chinese Acad Sci, Inst Microbiol, Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
[3] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China
[4] Sun Yat Sen Univ, Sch Med, Shenzhen Campus, Shenzhen 518107, Peoples R China
[5] Shanghai Inst Organ Chem, Ctr Excellence Mol Synth, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China
[6] Capital Med Univ, Sch Basic Med Sci, Dept Pathogen Microbiol, Beijing 100069, Peoples R China
[7] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin 300308, Peoples R China
来源
SMALL SCIENCE | 2022年 / 2卷 / 06期
基金
中国国家自然科学基金;
关键词
3C-like protease; Oridonin; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); traditional Chinese medicine; virus inhibitor;
D O I
10.1002/smsc.202100124
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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.
引用
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页数:10
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