Stefanik et al.
FDA-approved drugs efavirenz, tipranavir, and dasabuvir inhibit replication of multiple flaviviruses in Vero cells.
Microorganisms 2020;8(4):E599, doi: 10.3390/microorganisms8040599
No approved effective antiviral therapy directed against flaviviruses is currently available. The authors performed a silico screening of a library of FDA-approved antiviral drugs for their interaction with Zika virus (ZIKV) proteins NS3 (helicase and protease) and NS5 (RNA-dependent RNA polymerase and methyltransferase).
From a total of 1960 FDA-approved drugs, 73 were identified as FDA-approved antiviral drugs and 12 were identified with favorable docking scores. These 12 in sicilco selected drugs were then tested in-vitro for an anti ZIKV effect on Vero cells at a concentration of 50 µM. Three compounds reduced ZIKV titer in culture at the above-mentioned concentration: efavirenz, tipanavir and dasubuvir. The antiviral effect was also seen when the drugs were applied 2 hours post infection. Then, the authors evaluated the cytotoxic profiles and antiviral potency of the drugs in three different cell lines and in target cells like human neuroblastoma cells. Overall, efavirenz, tipranavir and dasabuvir at micromolar concentrations were identified to inhibit two representatives of mosquito-borne flaviviruses (ZIKV and WNV) and one representative of flaviviruses transmitted by ticks (TBE virus). These results indicate novel activities of the three drugs, and it is warranted to continue research on these drugs either individually or in combination.
Mode of action of FDA-approved antiviral drugs
Efavirenz: targets HIV reverse transcriptase
Tipranavir: an inhibitor of HIV protease
Dasabuvir: an inhibitor of HCV NS5B polymerase stopping replication