In vitro susceptibility of geographically and temporally distinct Zika viruses to favipiravir and ribavirin

Background: Zika virus, a previously neglected mosquitoborne virus, is prompting worldwide concern because of its connection with congenital defects, Guillain-Barre syndrome, meningoencephalitis and myelitis in infected individuals. However, no specific antiviral therapy is available at present. In this study, we investigated the in vitro susceptibility of geographically and temporally distinct Zika viruses against the RNA polymerase inhibitors, favipiravir (T-705) and ribavirin. Methods: The in vitro activity of each drug and a 1: 1 mixture combination was assessed against five geographically and temporally distinct Zika strains by plaque reduction assay (PRA), the gold standard phenotypic method. Results: We showed that both drugs exhibit in vitro inhibitory activity against five different Zika strains isolated in different years and continents, with mean 50% inhibitory concentration (IC50) values of 35 +/- 14 and 35 +/- 20 mu M, respectively, by PRA. We did not observe a synergistic effect when both drugs were combined at the equimolar concentration (IC50 = 33 +/- 11 mu M). Conclusions: These results indicate that T-705 has the potential to be used in patients with complicated diseases and/or those individuals presenting with significant comorbidities.