Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro
文献类型： 外文期刊
作者： Zhou, Shuting 1 ; Zhu, Junrui 3 ; Zhao, Houde 1 ; Huang, Zixin 1 ; Zheng, Kangqi 1 ; Xia, Fan 4 ; Xu, Yufan 1 ; Zhao, Guocheng 1 ; Jiang, Jijie 1 ; Zhang, En 2 ; Nian, Haoyang 2 ; Cui, Li 2 ; Sun, Tao 2 ; Wang, Xiangfeng 4 ; Zhou, Yanjun 3 ; Yang, Zhibiao 1 ; Wang, Zhe 1 ;
作者机构： 1.Shanghai Jiao Tong Univ, Shanghai Collaborat Innovat Ctr Agriseeds, Sch Agr & Biol, Shanghai 200240, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai Key Lab Vet Biotechnol, Shanghai 200240, Peoples R China
3.Chinese Acad Agr Sci, Dept Swine Infect Dis, Shanghai Vet Res Inst, Shanghai 200241, Peoples R China
4.China Agr Univ, Coll Agron & Biotechnol, Beijing 100094, Peoples R China
关键词： Porcine epidemic diarrhea virus; (PEDV); Clofazimine (CFZ); Spike; RdRp; Inactivation
期刊名称：VIROLOGICA SINICA （ 影响因子：4.0； 五年影响因子：4.1 ）
ISSN： 1674-0769
年卷期： 2025 年 40 卷 3 期
页码：
收录情况： SCI
摘要： 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 0.1364 mu M. 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.
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