Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection

Emerging RNA virus outbreaks, including Zika virus, highlight the urgent need for novel antiviral strategies. Zika virus, a positive-strand RNA virus, causes congenital Zika syndrome, and to date, there are no approved vaccines or antiviral treatments. In this context, microRNAs are small non-coding RNAs that regulate gene expression and show potential as antiviral agents due to their ability to target viral RNA, making them a promising therapeutic approach against Zika syndrome. In this study, we identified endogenous microRNAs that interact with the virus genome using computational algorithms and overexpressed them in VERO cells. Twelve microRNAs reduced viral cytopathic effects by more than 50% in cells infected with a Brazilian Zika virus strain. Additionally, we used a computational platform to select pharmacological compounds capable of modulating endogenous microRNAs in human cells, achieving over 90% inhibition of Zika virus activity. These findings offer a promising path through drug repurposing for antiviral therapy by modulating endogenous microRNAs, with potential applications for other positive-strand RNA viruses.