2. Academic Validation
  3. Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro

Clofazimine targeting the spike protein and RdRp exhibits highly efficient antiviral activity against porcine epidemic diarrhea virus in vitro

  • Virol Sin. 2025 Jun;40(3):477-490. doi: 10.1016/j.virs.2025.05.012.
Shuting Zhou 1,  Junrui Zhu 2,  Houde Zhao 1,  Zixin Huang 1,  Kangqi Zheng 1,  Fan Xia 3,  Yufan Xu 1,  Guocheng Zhao 1,  Jijie Jiang 1,  En Zhang 4,  Haoyang Nian 4,  Li Cui 4,  Tao Sun 4,  Xiangfeng Wang 3,  Yanjun Zhou 2,  Zhibiao Yang 5,  Zhe Wang 6
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
  • 3 College of Agronomy and Biotechnology, China Agricultural University, Beijing, 100094, China.
  • 4 Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 5 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. Electronic address: zbyang@sjtu.edu.cn.
  • 6 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. Electronic address: wangz@sjtu.edu.cn.
PMID: 40460916 DOI: 10.1016/j.virs.2025.05.012
Abstract

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 ​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.

Keywords

Clofazimine (CFZ); Inactivation; Porcine epidemic diarrhea virus (PEDV); RdRp; Spike.

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