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

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

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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.

SARS-CoV-2OridoninAntiviralProtease inhibitor

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

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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

Hunan Normal University,School of Medicine,Changsha,410081,China

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Creative Research Group Program of Natural Science Foundation of Hubei ProvinceChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Hubei Province,China

2022CFA0212022M7208953210011322001322017CFB535

2023

10.1016/j.virs.2023.04.008

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
年,卷(期)：2023.38(3)
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