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
收藏
页数:10
相关论文
共 50 条
  • [21] Structural differences in 3C-like protease (Mpro) from SARS-CoV and SARS-CoV-2: molecular insights revealed by Molecular Dynamics Simulations
    Meet Parmar
    Ritik Thumar
    Bhumi Patel
    Mohd Athar
    Prakash C. Jha
    Dhaval Patel
    Structural Chemistry, 2023, 34 : 1309 - 1326
  • [22] Structural differences in 3C-like protease (Mpro) from SARS-CoV and SARS-CoV-2: molecular insights revealed by Molecular Dynamics Simulations
    Parmar, Meet
    Thumar, Ritik
    Patel, Bhumi
    Athar, Mohd
    Jha, Prakash C.
    Patel, Dhaval
    STRUCTURAL CHEMISTRY, 2023, 34 (04) : 1309 - 1326
  • [23] Production of a functionally active recombinant SARS-CoV-2 (COVID-19) 3C-like protease and a soluble inactive 3C-like protease-RBD chimeric in a prokaryotic expression system
    De Marco Verissimo, Carolina
    Lopez Corrales, Jesus
    Dorey, Amber L.
    Cwiklinski, Krystyna
    Lalor, Richard
    Calvani, Nichola Eliza Davies
    Jewhurst, Heather L.
    Flaus, Andrew
    Doyle, Sean
    Dalton, John P.
    EPIDEMIOLOGY AND INFECTION, 2022, 150
  • [24] Ugonin J Acts as a SARS-CoV-2 3C-like Protease Inhibitor and Exhibits Anti-inflammatory Properties
    Chiou, Wei-Chung
    Lu, Hsu-Feng
    Hsu, Nung-Yu
    Chang, Tein-Yao
    Chin, Yuan-Fan
    Liu, Ping-Cheng
    Lo, Jir-Mehng
    Wu, Yeh B.
    Yang, Jinn-Moon
    Huang, Cheng
    FRONTIERS IN PHARMACOLOGY, 2021, 12
  • [25] SARS-CoV-2 3C-like protease antagonizes interferon-beta production by facilitating the degradation of IRF3
    Zhang, Wenwen
    Ma, Zhenling
    Wu, Yaru
    Shi, Xixi
    Zhang, Yanyan
    Zhang, Min
    Zhang, Menghao
    Wang, Lei
    Liu, Wei
    CYTOKINE, 2021, 148
  • [26] Potent inhibitors of SARS-CoV-2 3C-like protease derived from N-substituted isatin compounds
    Liu, Pei
    Liu, Hongbo
    Sun, Qi
    Liang, Hao
    Li, Chunmei
    Deng, Xiaobing
    Liu, Ying
    Lai, Luhua
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 206
  • [27] Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2
    Yan, Yong
    Liu, Hanwen
    Wu, Di
    Gu, Zhihao
    Guo, Wenhao
    Yao, Hequan
    Lin, Kejiang
    Li, Xuanyi
    FUTURE MEDICINAL CHEMISTRY, 2024, 16 (09) : 887 - 903
  • [28] Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease
    Sun, Qi
    Ye, Fei
    Liang, Hao
    Liu, Hongbo
    Li, Chunmei
    Lu, Roujian
    Huang, Baoying
    Zhao, Li
    Tan, Wenjie
    Lai, Luhua
    SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2021, 6 (01)
  • [29] Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease
    Qi Sun
    Fei Ye
    Hao Liang
    Hongbo Liu
    Chunmei Li
    Roujian Lu
    Baoying Huang
    Li Zhao
    Wenjie Tan
    Luhua Lai
    Signal Transduction and Targeted Therapy, 6
  • [30] In silico studies of natural products from medicinal plants to identify potential inhibitors for SARS-CoV-2 3C-like protease
    Nguyen Tan Khanh
    Tran Thanh Hoa
    VIETNAM JOURNAL OF CHEMISTRY, 2021, 59 (05) : 557 - 562