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 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

作者机构：Virus LaboratoryInstitute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou510623China Key Laboratory of Special Pathogens and BiosafetyWuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Chinese Academy of SciencesBeijing100049China Hunan Normal UniversitySchool of MedicineChangsha410081China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2023年第38卷第3期

页      面：470-479页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

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) 

主　　题：SARS-CoV-2 Oridonin Antiviral Protease inhibitor 

摘      要：COVID-19 has become a global public health crisis since its outbreak in China in December *** there are few clinically effective drugs to combat SARS-CoV-2 *** 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 ***,we investigated the antiviral activity of oridonin,a natural small-molecule compound,against SARS-CoV-2 infection in *** time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry ***,the inhibition of viral replication by oridonin depends on the oxidation activity ofα,β-unsaturated *** 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 *** 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 ***,our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.