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The Zika virus (ZIKV) remains a global health concern. Thus far, no antiviral or vaccine has been approved to prevent or treat ZIKV infection. In a previous study, we found that lipophilic statins can inhibit ZIKV production in Vero cells. These statins appear to have different potencies against ZIKV infection. Here, we determined whether combinations of statins would have synergistic effects to maximize the efficacy of the statins and to reduce potential side effects. Specifically, we used a modified fixed-ratio assay for the combinations of atorvastatin (ATO) or fluvastatin (FLU) with mevastatin (MEV) or simvastatin (SIM). All combinations with MEV tended towards synergy, especially with higher fractions of MEV in the combinations. The ATO + SIM combination tended towards additivity. The FLU + SIM combination also tended towards additivity except for one combination which had the highest fraction of FLU over SIM among the tested combinations. Overall, certain combinations of ATO or FLU with SIM or MEV may be synergistic. More exhaustive combinatorial assays in vitro and in vivo could help define whether combining lipophilic statins would be beneficial and safe for treating ZIKV infections.

Effects of Statin Combinations on Zika Virus Infection in Vero Cells