Antiviral effect of silymarin against Zika virus in vitro

Zika virus (ZIKV) epidemic and its association with severe neurological syndromes have raised worldwide concern. Despite the great clinical relevance of this infection, no vaccine or specific treatment is available and the search for antiviral compounds against ZIKV is extremely necessary. Several natural compounds, such as silymarin, exhibit antioxidant, hepatoprotective, and antiviral properties; however, the antiviral potential of this compound remains partially investigated. Therefore, the objective of this study was to evaluate in vitro the antiviral activity of silymarin against ZIKV infection. Global antiviral activity, dose-dependent, plaque reduction, and time-of-drug-addition assays were used to determine the anti-ZIKV activity of silymarin. Additionally, to start characterizing the mechanisms of action we determined whether silymarin could have a virucidal effect and inhibit viral adsorption and penetration stages. Regarding its global antiviral activity, silymarin showed significant inhibition of ZIKV infection, protecting cells infected with EC₅₀ equal to 34.17μg/mL, with a selectivity index greater than 17 and 4x greater than that of the positive control (ribavirin). Its greatest efficiency was achieved at 125μg/mL, whose cell viability did not differ from the control without infection and treatment. Furthermore, treatment with silymarin reduced viral load by up to two logs (> 90%) concerning viral control, when evaluating virucidal activity and the precocious times of infection. Thus, our results set to show the promising anti-ZIKV activity of silymarin, which does not seem to have a single inhibition mechanism, acting at different times of infection, and still has the advantage of silymarin be a phytotherapy already available on the market.