Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors.

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 CZ 613 00 Brno Czech Republic

Department of Pharmaceutical and Medicinal Chemistry Faculty of Pharmaceutical Sciences Nnamdi Azikiwe University PMB 5025 Awka 420281 Nigeria

Department of Virology Veterinary Research Institute Hudcova 70 CZ 62100 Brno Czech Republic

Faculty of Science Masaryk University Kamenice 5 CZ 625 00 Brno Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Branisovska 31 CZ 37005 Ceske Budejovice Czech Republic

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