In Vitro Antiviral Activity of Ribavirin against Severe Fever with Thrombocytopenia Syndrome Virus

Abstract

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus called SFTS virus (SFTSV). No effective antiviral therapy is available yet, but ribavirin (RBV) was used for patients with SFTS. We investigated the antiviral effect of RBV against SFTSV in vitro.

Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (0 - 500 μg/mL, in serial two-fold dilutions) and analyzed by cell viability MTS assay. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 tissue culture infective dose (TCID50) per well in a 96-well plate, and RBV was added at non-cytotoxic concentrations. The antiviral activity of RBV was determined by the observation of cytopathic effects by SFTSV-infected Vero cells and the measurement of viral RNA titers in culture supernatants using one-step real-time reverse transcription - polymerase chain reaction to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukeys post hoc test.

Results: Cytotoxicity due to RBV was not detected for RBV at concentrations ≤ 31.3 μg/mL. Viral RNAs at 24 h post-RBV treatment were reduced by administration of increasing RBV concentrations (1 - 32 μg/mL), compared with those of mock-treated cells (P < 0.01). RBV reduced SFTSV titers and cytopathic effects in a dose-dependent manner, with half maximal inhibitory concentrations of 3.69 to 8.72 μg/mL.

Conclusion: Our study shows that RBV has in vitro antiviral effect against SFTSV in a dose-dependent manner. Further studies are warranted to evaluate the clinical efficacy of RBV in SFTS.