Zhou Shuting, Zhu Junrui, Zhao Houde, Huang Zixin, Zheng Kangqi, Xia Fan, Xu Yufan, Zhao Guocheng, Jiang Jijie, Zhang En, Nian Haoyang, Cui Li, Sun Tao, Wang Xiangfeng, Zhou Yanjun, Yang Zhibiao, Wang Zhe
Shanghai Collaborative Innovation Center of Agri-Seeds / School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China; Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
Virol Sin. 2025 Jun;40(3):477-490. doi: 10.1016/j.virs.2025.05.012. Epub 2025 Jun 1.
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 IC value of 0.1364 μM. 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 post-infection (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.
猪流行性腹泻病毒（PEDV）感染可导致新生仔猪急性水样腹泻，给养猪业造成重大经济损失。本研究表明，氯法齐明（CFZ）在体外以剂量依赖的方式显著抑制PEDV复制，且细胞毒性可忽略不计。我们的添加时间试验结果表明，CFZ有效破坏病毒感染周期的多个阶段。使用CoV-RdRp-Gluc报告系统，我们评估了CFZ对PEDV RNA依赖性RNA聚合酶（RdRp）的效力，并确定其低IC值为0.1364 μM。分子对接研究进一步证实，CFZ在PEDV的刺突蛋白和RdRp蛋白的活性位点具有高结合亲和力。对经CFZ处理和未经处理的Vero E6细胞进行转录组分析，发现在感染后8小时（hpi）转录活性有显著变化。此外，CFZ与核苷类似物同时应用在体外增强了CFZ的抗PEDV效果。我们的研究强调了CFZ作为一种可行的抗PEDV治疗剂的潜力。
