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Currently, there are no available vaccines or specific treatments against JCV infections.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p>The antiviral efficacy of favipiravir (FPV) against JCV infection was evaluated <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> in comparison with that of ribavirin (RBV) and 2\u2019-fluoro-2\u2019-deoxycytidine (2\u2019-FdC). The <jats:italic>in vitro<\/jats:italic> inhibitory effect of these drugs on JCV replication was evaluated in Vero and Neuro-2a (N2A) cells. The efficacy of FPV in the treatment of JCV infection <jats:italic>in vivo<\/jats:italic> was evaluated in C57BL\/6J mice inoculated intracerebrally with JCV, as per the survival, viral titers in the brain, and viral RNA load in the blood. The 90% inhibitory concentrations (IC<jats:sub>90<\/jats:sub>) of FPV, RBV, and 2\u2019-FdC were 41.0, 61.8, and 13.6 \u03bcM in Vero cells and 20.7, 25.8, and 8.8 \u03bcM in N2A cells, respectively. All mice infected with 1.0\u00d710<jats:sup>4<\/jats:sup> TCID<jats:sub>50<\/jats:sub> died or were sacrificed within 10 days post-infection (dpi) without treatment. However, mice treated with FPV for 5 days [initiated either 2 days prior to infection (\u22122 dpi\u20132 dpi) or on the day of infection (0 dpi\u20134 dpi)] survived significantly longer than control mice, administered with PBS (p = 0.025 and 0.011, respectively). Moreover, at 1 and 3 dpi, the virus titers in the brain were significantly lower in FPV-treated mice (0 dpi\u20134 dpi) <jats:italic>versus<\/jats:italic> PBS-treated mice (p = 0.002 for both 1 and 3 dpi).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>Although the intracerebral inoculation route is thought to be a challenging way to evaluate drug efficacy, FPV inhibits the <jats:italic>in vitro<\/jats:italic> replication of JCV and prolongs the survival of mice intracerebrally inoculated with JCV. These results will enable the development of a specific antiviral treatment against JCV infections and establishment of an effective animal model.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0009553","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T18:30:40Z","timestamp":1625250640000},"page":"e0009553","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon 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