Rosa Rhubia S M, Palameta Soledad, Toscaro Jessica M, Miller Michael E, Lopes-de-Oliveira Paulo S, Bajgelman Marcio C
Brazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo, Brazil.
Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Mol Ther Nucleic Acids. 2025 May 14;36(2):102562. doi: 10.1016/j.omtn.2025.102562. eCollection 2025 Jun 10.
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.
包括寨卡病毒在内的新出现的RNA病毒疫情凸显了对新型抗病毒策略的迫切需求。寨卡病毒是一种正链RNA病毒，可导致先天性寨卡综合征，迄今为止，尚无获批的疫苗或抗病毒治疗方法。在此背景下，微小RNA是一类调节基因表达的小型非编码RNA，由于其能够靶向病毒RNA而显示出作为抗病毒剂的潜力，使其成为治疗寨卡综合征的一种有前景的方法。在本研究中，我们使用计算算法鉴定了与病毒基因组相互作用的内源性微小RNA，并在VERO细胞中过表达它们。12种微小RNA在感染巴西寨卡病毒株的细胞中使病毒细胞病变效应降低了50%以上。此外，我们使用一个计算平台来选择能够调节人类细胞内源性微小RNA的药理化合物，实现了对寨卡病毒活性超过90%的抑制。这些发现为通过调节内源性微小RNA进行药物再利用以进行抗病毒治疗提供了一条有前景的途径，对其他正链RNA病毒也有潜在应用价值。
