Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever
Figure 5
Treatment of CCHFV-infected IFNAR−/− mice with ribavirin and arbidol hydrochloride.
Mice were inoculated i.p. with 10, 100, or 1,000 FFU of virus. Ribavirin was administered i.p. once daily. Animals received a ribavirin dose of 100/(kg×d) or 0.9% NaCl as a placebo. Treatment was commenced 1 h p.i. and continued until death or day 8. Arbidol was administered once daily per os using a stomach probe. Animals received an arbidol dose of 150 mg/(kg×d) or 0.5% methylcellulose as a placebo. Treatment was commenced 1 day before infection and continued until death or day 8. Organ titers were determined in animals that succumbed to the infection or had to be euthanized due to the severity of the disease. In addition, three animals from the ribavirin-treated group were randomly euthanized at day 3 p.i. to determine the virus titer in organs (weight, AST, ALT, and viremia data obtained from these mice until day 3 were included in the respective graphs). Mean and standard deviation are shown for weight and log-transformed organ titers. Vertical bars in the graphs for AST and ALT (note the log scale of the y-axis) and the log-transformed virus titers in blood represent the mean values. The duration of treatment in the survival plots, the range of viremia below the detection limit of the immunofocusassay as well as the normal reference range of AST and ALT in mice [59] are shaded in grey. Notes. 100 FFU placebo group: The animal, which died at day 6, showed no AST/ALT elevation and viremia at day 4. 100 FFU ribavirin group: The surviving animal did not show detectable viremia, but AST elevation. Viremia was not determined at day 11. 10 FFU arbidol group: The surviving animal had no AST elevation and viremia at day 4. Some values for days 4, 8, and, 11 were not determined due to insufficient amount of blood.