The FDA-approved drug sofosbuvir inhibits Zika virus infection

•Sofosbuvir reduces replication of multiple ZIKV isolates in human liver and placental cells.•Sofosbuvir protects human neuronal stem cells from ZIKV infection.•Oral administration of sofosbuvir via drinking reduces ZIKV death in mice.•Sofosbuvir should be evaluated as an anti-ZIKV treatment in non-rodent species.

The rapidly expanding Zika virus (ZIKV) epidemic has affected thousands of individuals with severe cases causing Guillain-Barré syndrome, congenital malformations, and microcephaly. Currently, there is no available vaccine or therapy to prevent or treat ZIKV infection. We evaluated whether sofosbuvir, an FDA-approved nucleotide polymerase inhibitor for the distantly related hepatitis C virus, could have antiviral activity against ZIKV infection. Cell culture studies established that sofosbuvir efficiently inhibits replication and infection of several ZIKV strains in multiple human tumor cell lines and isolated human fetal-derived neuronal stem cells. Moreover, oral treatment with sofosbuvir protected against ZIKV-induced death in mice. These results suggest that sofosbuvir may be a candidate for further evaluation as a therapy against ZIKV infection in humans.