Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus  

作　　者：Mengxin Zhou Yutong Han Mengxia Li Gang Ye Guiqing Peng 

机构地区：[1]State Key Laboratory of Agricultural Microbiology,College of Veterinary Medicine,Huazhong Agricultural University,Wuhan,430070,China [2]Key Laboratory of Preventive Veterinary Medicine in Hubei Province,The Cooperative Innovation Center for Sustainable Pig Production,Wuhan,430070,China

出　　处：《Virologica Sinica》2021年第6期1421-1430,共10页中国病毒学（英文版）

基　　金：This work was supported by the National Key R&D Plan of China(grant no.2018YFD0500102);the Natural Science Foundation of Hubei Province of China(grant no.2016CFA069)。

摘　　要：Coronaviruses(CoVs)are important human and animal pathogens that cause respiratory and gastrointestinal diseases.Porcine epidemic diarrhoea(PED),characterized by severe diarrhoea and vomiting in pigs,is a highly lethal disease caused by porcine epidemic diarrhoea virus(PEDV)and causes substantial losses in the swine industry worldwide.However,currently available commercial drugs have not shown great therapeutic effects.In this study,a fluorescence resonance energy transfer(FRET)-based assay was applied to screen a library containing 1,590 compounds and identified two compounds,3-(aminocarbonyl)-1-phenylpyridinium and 2,3-dichloronaphthoquinone,that target the 3C-like protease(3CL^(pro))of PEDV.These compounds are of low molecular weight(MW)and greatly inhibited the activity of this enzyme(IC_(50) values were obtained in this study).Furthermore,these compounds exhibited antiviral capacity against another member of the CoV family,feline infectious peritonitis virus(FIPV).Here,the inhibitory effects of these compounds against CoVs on Vero cells and feline kidney cells were identified(with EC_(50) values)and cell viability assays were performed.The results of putative molecular docking models indicate that these compounds,labeled compound 1 and compound 2,contact the conserved active sites(Cys144,Glu165,Gln191)of 3CL^(pro) via hydrogen bonds.These findings provide insight into the antiviral activities of compounds 1 and 2 that may facilitate future research on anti-CoV drugs.

关 键 词：Coronavirus(CoVs) Inhibitor 3C-like Protease Porcine epidemic diarrhoea virus(PEDV) Feline infectious peritonitis virus(FIPV) 

分 类 号：S859.7[农业科学—临床兽医学]