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

Author(s)

Rosa, Rhubia S. M. ; Palameta, Soledad ; Toscaro, Jessica M. ; Miller, Michael E. ; Lopes-de-Oliveira, Paulo S. ; Bajgelman, Marcio C.

• Document type: Journal article
• Source: MOLECULAR THERAPY-NUCLEIC ACIDS; v. 36, n. 2, p. 12-pg., 2025-06-10.

Abstract

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 micro-RNAs 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 re-purposing for antiviral therapy by modulating endogenous microRNAs, with potential applications for other positive-strand RNA viruses. (AU)

• FAPESP's process: 21/09107-9 - Development of a Treg Immunotherapy approach based on chimeric aptamers to potentiate antitumor vaccines
• Grantee: Marcio Chaim Bajgelman
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/12245-0 - Exploring therapeutic benefit of immunomodulatory vaccines derived from genetically modified human cells, to potentiate antitumor response in triple negative breast cancer model
• Grantee: Marcio Chaim Bajgelman
• Support Opportunities: Regular Research Grants