TY - JOUR T1 - The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication JF - bioRxiv DO - 10.1101/061671 SP - 061671 AU - Caroline Q. Sacramento AU - Gabrielle R. de Melo AU - Natasha Rocha AU - Lucas Villas Bôas Hoelz AU - Milene Mesquita AU - Caroline S. de Freitas AU - Natalia Fintelman Rodrigues AU - Andressa Marttorelli AU - André C. Ferreiral AU - Giselle Barbosa-Lima AU - Mônica M. Bastos AU - Eduardo de Mello Volotão AU - Diogo A. Tschoeke AU - Luciana Leomil AU - Fernando A. Bozza AU - Patrícia T. Bozza AU - Nubia Boechat AU - Fabiano L. Thompson AU - Ana M. B. de Filippis AU - Karin Brüning AU - Thiago Moreno L. Souza Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/06/061671.abstract N2 - Zika virus (ZIKV) is a member of Flaviviridae family, as other agents of clinical significance, such as dengue (DENV) and hepatitis C (HCV) viruses. ZIKV spread from Africa to Pacific and South American territories, emerging as an etiological pathogen of neurological disorders, during fetal development and in adulthood. Therefore, antiviral drugs able to inhibit ZIKV replication are necessary. Broad spectrum antivirals, such as interferon, ribavirin and favipiravir, are harmful for pregnant animal models and women. The clinically approved uridine nucleotide analog anti-HCV drug, sofosbuvir, has not been affiliated to teratogenicity. Sofosbuvir target the most conserved protein over the members of the Flaviviridae family, the viral RNA polymerase. We thus studied ZIKV susceptibility to sofosbovir. We initially characterized a Brazilian ZIKV strain for use in experimental assays. Sofosbuvir inhibits the Brazilian ZIKV replication in a dose-dependent manner, both in BHK-21 cells and SH-Sy5y, by targeting ZIKV RNA polymerase activity, with the involvement of conserved amino acid residues over the members of Flaviviridae family. The identification of clinically approved antiviral drugs endowed with anti-ZIKV could reduce the time frame in pre-clinical development. Altogether, our data indicates that sofosbuvir chemical structure is endowed with anti-ZIKV activity. ER -