Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)signi...Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.展开更多
基金supported by a grant from the National Key Research and Development Plans of China(No.2021YFD1800401)to Zhe Wangthe National Natural Science Foundation of China(No.32070128)to Zhe Wang+5 种基金the Shanghai Biomedical Science and Technology Support Special Project(No.21S11900200)to Zhe Wangthe National Natural Science Foundation of China(No.31472211)to ZhiBiao Yangthe Natural Science Foundation of Shanghai(No.21ZR1433900)to Zhibiao Yangthe National Key Research and Development Program of China(No.2022YFD1800805)to Yanjun Zhouthe Pinduoduo-China Agricultural University Research Fund(PC2024A01003)to Xiangfeng Wangthe Biomedicine and Technology Supporting Project of the Shanghai Science and Technology Innovation Plan(Grant No.22S11902200,China)to Tao Sun.
文摘Porcine epidemic diarrhea virus(PEDV)infection causes acute watery diarrhea in neonatal piglets,leading to substantial economic losses within the pig farming industry.This study demonstrates that clofazimine(CFZ)significantly inhibits PEDV replication in a dose-dependent manner in vitro,with negligible cytotoxicity.Findings from our time-of-addition assays indicate that CFZ effectively disrupts multiple stages of the viral infection cycle.Using a CoV-RdRp-Gluc reporter system,we evaluated the potency of CFZ against PEDV RNA-dependent RNA polymerase(RdRp),and determined a low IC50 value of 0.1364μM.Molecular docking studies further confirmed that CFZ has high binding affinity at the active sites of the spike protein and RdRp protein in PEDV.Transcriptome analysis of Vero E6 cells,with and without CFZ treatment,revealed a significant change in transcriptional activity at 8 h postinfection(hpi).Moreover,the simultaneous application of CFZ and nucleoside analogs showed enhanced the anti-PEDV effect of CFZ in vitro.Our study underscores the potential of CFZ as a viable therapeutic agent against PEDV.
