Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization  

作　　者：Yue Wang Huimin Huang Dongliang Li Chenxu Zhao Shuai Li Panpan Qin Yaqin Li Xia Yang Wenjuan Du Wentao Li Yongtao Li 

机构地区：[1]College of Veterinary Medicine,Henan Agricultural University,Zhengzhou,450002,China [2]State Key Laboratory of Agricultural Microbiology,College of Veterinary Medicine,Huazhong Agricultural University,Wuhan,430070,China [3]Faculty of Veterinary Medicine,Utrecht University,Utrecht,3584 CL,the Netherlands [4]Hubei Hongshan Laboratory,Wuhan,430070,China

出　　处：《Virologica Sinica》2023年第2期296-308,共13页中国病毒学（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.31602033 and 32172839);the China Scholarship Council under grant 201908410129.

摘　　要：Porcine epidemic diarrhea virus(PEDV),an enteropathogenic coronavirus,has catastrophic impacts on the global pig industry.However,there remain no effective drugs against PEDV infection.In this study,we utilized a recombinant PEDV expressing renilla luciferase(PEDV-Rluc)to screen potential anti-PEDV agents from an FDAapproved drug library in Vero cells.Four compounds were identified that significantly decreased luciferase activity of PEDV-Rluc.Among them,niclosamide was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index.It can efficiently inhibit viral RNA synthesis,protein expression and viral progeny production of classical and variant PEDV strains in a dose-dependent manner.Time of addition assay showed that niclosamide exhibited potent anti-PEDV activity when added simultaneously with or after virus infection.Furthermore,niclosamide significantly inhibited the entry stage of PEDV infection by affecting viral internalization rather than viral attachment to cells.In addition,a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide in vitro.Taken together,these findings suggested that niclosamide is a novel antiviral agent that might provide a basis for the development of novel drug therapies against PEDV and other related pathogenic coronavirus infections.

关 键 词：Coronavirus Porcine epidemic diarrhea virus(PEDV) Niclosamide(NIC) ANTIVIRAL Virus entry ENDOCYTOSIS Host-targeted antivirals 

分 类 号：S852.651[农业科学—基础兽医学]