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Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization.
Wang, Yue; Huang, Huimin; Li, Dongliang; Zhao, Chenxu; Li, Shuai; Qin, Panpan; Li, Yaqin; Yang, Xia; Du, Wenjuan; Li, Wentao; Li, Yongtao.
Afiliación
  • Wang Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Huang H; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Li D; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Zhao C; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Li S; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Qin P; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Li Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Yang X; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China.
  • Du W; Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the Netherlands.
  • Li W; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Hubei Hongshan Laboratory, Wuhan, 430070, China. Electronic address: wentao@mail.hzau.edu.cn.
  • Li Y; College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China; Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the Netherlands. Electronic address: yongtaole@126.com.
Virol Sin ; 38(2): 296-308, 2023 Apr.
Article en En | MEDLINE | ID: mdl-36702255
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there remain no effective drugs against PEDV infection. In this study, we utilized a recombinant PEDV expressing renilla luciferase (PEDV-Rluc) to screen potential anti-PEDV agents from an FDA-approved drug library in Vero cells. Four compounds were identified that significantly decreased luciferase activity of PEDV-Rluc. Among them, niclosamide was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index. It can efficiently inhibit viral RNA synthesis, protein expression and viral progeny production of classical and variant PEDV strains in a dose-dependent manner. Time of addition assay showed that niclosamide exhibited potent anti-PEDV activity when added simultaneously with or after virus infection. Furthermore, niclosamide significantly inhibited the entry stage of PEDV infection by affecting viral internalization rather than viral attachment to cells. In addition, a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide in vitro. Taken 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades de los Porcinos / Infecciones por Coronavirus / Virus de la Diarrea Epidémica Porcina Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Virol Sin Asunto de la revista: VIROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades de los Porcinos / Infecciones por Coronavirus / Virus de la Diarrea Epidémica Porcina Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Virol Sin Asunto de la revista: VIROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos