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

作　　者：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 

机构地区：[1]Virus Laboratory,Institute of Pediatrics,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,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 [3]University of Chinese Academy of Sciences,Beijing,100049,China [4]Hunan Normal University,School of Medicine,Changsha,410081,China

出　　处：《Virologica Sinica》2023年第3期470-479,共10页中国病毒学（英文版）

基　　金：the Creative Research Group Program of Natural Science Foundation of Hubei Province(2022CFA021);the China Postdoctoral Science Foundation(2022M720895);the National Natural Science Foundation of China(3210011 and 32200132);the Natural Science Foundation of Hubei Province,China(2017CFB535).

摘　　要：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(M^(pro)),papain-like protease(PL^(pro))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 ofα,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.

关 键 词：SARS-CoV-2 ORIDONIN ANTIVIRAL Protease inhibitor 

分 类 号：R285[医药卫生—中药学]