Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization
作者机构:College of Veterinary MedicineHenan Agricultural UniversityZhengzhou450002China State Key Laboratory of Agricultural MicrobiologyCollege of Veterinary MedicineHuazhong Agricultural UniversityWuhan430070China Faculty of Veterinary MedicineUtrecht UniversityUtrecht3584 CLthe Netherlands Hubei Hongshan LaboratoryWuhan430070China
出 版 物:《Virologica Sinica》 (中国病毒学(英文版))
年 卷 期:2023年第38卷第2期
页 面:296-308页
核心收录:
学科分类:090601[农学-基础兽医学] 09[农学] 0906[农学-兽医学]
基 金:supported by the National Natural Science Foundation of China(Grant No.31602033 and 32172839) the China Scholarship Council under grant 201908410129
主 题:Coronavirus Porcine epidemic diarrhea virus(PEDV) Niclosamide(NIC) Antiviral Virus entry Endocytosis Host-targeted antivirals
摘 要:Porcine epidemic diarrhea virus(PEDV),an enteropathogenic coronavirus,has catastrophic impacts on the global pig ***,there remain no effective drugs against PEDV *** 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 *** compounds were identified that significantly decreased luciferase activity of *** them,niclosamide was further characterized because it exhibited the most potent antiviral activity with the highest selectivity *** can efficiently inhibit viral RNA synthesis,protein expression and viral progeny production of classical and variant PEDV strains in a dose-dependent *** of addition assay showed that niclosamide exhibited potent anti-PEDV activity when added simultaneously with or after virus ***,niclosamide significantly inhibited the entry stage of PEDV infection by affecting viral internalization rather than viral attachment to *** addition,a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide in *** 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.