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Repurposing of clinically approved drugs appeared promising for rapidly identifying effective, safe, and readily available candidates for antiviral drugs. Here, we screened the small\u2010molecule compounds with anti\u2010WNV activity from 978 Food Drug Administration\u2010approved drugs. Four compounds, including cilnidipine, mycophenolate mofetil, nitazoxanide, and teriflunomide, were found to efficiently abrogate WNV infection in Vero cells and human neuroblastoma SH\u2010SY5Y cells. The four compounds also exert broad\u2010spectrum antiviral activity against the Zika virus, Japanese encephalitis virus, yellow fever virus, tick\u2010borne 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,\u00a0ML390 and vidofludimus, also displayed potent activity against WNV infection in vitro and in vivo.<\/jats:p>","DOI":"10.1002\/jmv.27891","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T02:54:35Z","timestamp":1653879275000},"page":"4918-4925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Identification of clinical candidates against West Nile virus by activity screening in vitro and effect evaluation in vivo"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-8852","authenticated-orcid":false,"given":"Hailin","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Naval Medicine Navy Medical University  Shanghai People's Republic of 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IP PORTAL.Vidofludimus for use in the treatment or prevention of viral diseases. 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