3 years ago

Antiviral activity of fenretinide against Zika virus

The rapid spread of Zika virus (ZIKV) in recent years has highlighted the severe diseases associated with ZIKV infection, such as Guillain-Barré syndrome in adults and microcephaly in newborns. Yet, no vaccines or antivirals currently exist to prevent or treat ZIKV infection. We and others have previously identified N-(4-hydroxyphenyl) retinamide (fenretinide or 4-HPR) as an antiviral compound that inhibits dengue virus 2 (DV2) and other flaviviruses by limiting the steady-state accumulation of viral RNA. Here we show that 4-HPR potently inhibits Zika virus (ZIKV) in mammalian cell culture and significantly reduces both serum viremia and brain viral burden in a murine model of ZIKV infection. Consistent with previous observations with dengue virus, this antiviral activity is associated with a significant reduction in the steady-state abundance of viral genomic RNA. We show this reduction is due to a major decrease in the rate of viral RNA synthesis, though not via direct inhibition of the activity of the viral replicase. These results establish 4-HPR's mode of action against DV and ZIKV and, taken with previous clinical trials that established 4-HPR's safety and tolerability, illustrate the potential utility of 4-HPR as an agent for treatment of ZIKV infection.

Publisher URL: www.sciencedirect.com/science

DOI: S0166354217306137

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