Mariana Baz1, Nathalie Goyette1, Bryan D Griffin2, Gary P Kobinger1,3, Guy Boivin1. 1. Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, QC, Canada. 2. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada. 3. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Abstract
BACKGROUND: Zika virus, a previously neglected mosquito-borne virus, is prompting worldwide concern because of its connection with congenital defects, Guillain-Barré 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 µM, respectively, by PRA. We did not observe a synergistic effect when both drugs were combined at the equimolar concentration (IC50 =33 ±11 µM). 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.
BACKGROUND:Zika virus, a previously neglected mosquito-borne virus, is prompting worldwide concern because of its connection with congenital defects, Guillain-Barré 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 µM, respectively, by PRA. We did not observe a synergistic effect when both drugs were combined at the equimolar concentration (IC50 =33 ±11 µM). 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.
Authors: Yong-Dae Gwon; Mårten Strand; Richard Lindqvist; Emma Nilsson; Michael Saleeb; Mikael Elofsson; Anna K Överby; Magnus Evander Journal: Viruses Date: 2020-03-22 Impact factor: 5.048