中国病毒学2023，Vol.38Issue(3) ：470-479.DOI:10.1016/j.virs.2023.04.008

Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase

Zherui Zhang Hongqing Zhang Yanan Zhang Qiuyan Zhang Qiaojie Liu Yanyan Hu Xiaoling Chen Jing Wang Yujia Shi Chenglin Deng Peng Gong Bo Zhang Xiaodan Li Bing Zhu Hanqing Ye
中国病毒学2023，Vol.38Issue(3) ：470-479.DOI:10.1016/j.virs.2023.04.008
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Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase

Zherui Zhang 1Hongqing Zhang 2Yanan Zhang 1Qiuyan Zhang 3Qiaojie Liu 3Yanyan Hu 2Xiaoling Chen 2Jing Wang 2Yujia Shi 4Chenglin Deng 3Peng Gong 2Bo Zhang 5Xiaodan Li 4Bing Zhu 6Hanqing Ye3
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作者信息

  • 1. Virus Laboratory,Institute of Pediatrics,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China;Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China
  • 2. Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China;University of Chinese Academy of Sciences,Beijing,100049,China
  • 3. Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China
  • 4. Hunan Normal University,School of Medicine,Changsha,410081,China
  • 5. Virus Laboratory,Institute of Pediatrics,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China;Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China;University of Chinese Academy of Sciences,Beijing,100049,China
  • 6. Virus Laboratory,Institute of Pediatrics,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China
  • 折叠

Abstract

COVID-19 has become a global public health crisis since its outbreak in China in December 2019.Currently there are few clinically effective drugs to combat SARS-CoV-2 infection.The main protein(Mpro),papain-like protease(PLpro)and RNA-dependent RNA polymerase(RdRp)of SARS-CoV-2 are involved in the viral replication,and might be prospective targets for anti-coronavirus drug development.Here,we investigated the antiviral activity of oridonin,a natural small-molecule compound,against SARS-CoV-2 infection in vitro.The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage.Mechanistically,the inhibition of viral replication by oridonin depends on the oxidation activity of α,β-unsaturated carbonyl.Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity,but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations.In particular,oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants(BA.1 and BA.2),which highlights its potential as a pan-coronavirus antiviral agent.Overall,our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.

Key words

SARS-CoV-2/Oridonin/Antiviral/Protease inhibitor

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基金项目

Creative Research Group Program of Natural Science Foundation of Hubei Province(2022CFA021)

China Postdoctoral Science Foundation(2022M720895)

National Natural Science Foundation of China(3210011)

National Natural Science Foundation of China(32200132)

Natural Science Foundation of Hubei Province,China(2017CFB535)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
参考文献量41
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