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Identification of clinical candidates against West Nile virus by activity screening in vitro and effect evaluation in vivo.
Tang, Hailin; Liu, Yang; Ren, Ruiwen; Liu, Yan; He, Yanhua; Qi, Zhongtian; Peng, Haoran; Zhao, Ping.
Afiliación
  • Tang H; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • Liu Y; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • Ren R; Center for Disease Control and Prevention of Southern Theater Command, Guangdong Guangzhou, People's Republic of China.
  • Liu Y; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • He Y; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • Qi Z; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • Peng H; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
  • Zhao P; Department of Microbiology, Faculty of Naval Medicine, Navy Medical University, Shanghai, People's Republic of China.
J Med Virol ; 94(10): 4918-4925, 2022 10.
Article en En | MEDLINE | ID: mdl-35644833
The West Nile virus (WNV) is a member of the flavivirus and is known to cause encephalitis. There is currently no specific treatment for WNV infection. Repurposing of clinically approved drugs appeared promising for rapidly identifying effective, safe, and readily available candidates for antiviral drugs. Here, we screened the small-molecule compounds with anti-WNV activity from 978 Food Drug Administration-approved drugs. Four compounds, including cilnidipine, mycophenolate mofetil, nitazoxanide, and teriflunomide, were found to efficiently abrogate WNV infection in Vero cells and human neuroblastoma SH-SY5Y cells. The four compounds also exert broad-spectrum antiviral activity against the Zika virus, Japanese encephalitis virus, yellow fever virus, tick-borne encephalitis virus, and chikungunya virus. Furthermore, nitazoxanide (a synthetic benzamide) and teriflunomide (an inhibitor of dihydroorotate dehydrogenase, DHODH) protected 20% and 40% of mice from lethal WNV challenge, respectively. Both drugs, which are orally bioavailable and have been approved clinically for many years, may be promising therapeutics for WNV infection. Moreover, the other two DHODH inhibitors, ML390 and vidofludimus, also displayed potent activity against WNV infection in vitro and in vivo.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fiebre del Nilo Occidental / Virus del Nilo Occidental / Flavivirus / Virus Zika / Infección por el Virus Zika / Neuroblastoma Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: J Med Virol Año: 2022 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fiebre del Nilo Occidental / Virus del Nilo Occidental / Flavivirus / Virus Zika / Infección por el Virus Zika / Neuroblastoma Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: J Med Virol Año: 2022 Tipo del documento: Article