biostudies-literatureBie YChinese Academy of SciencesMinistry of Science and Technology of the People's Republic of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of China645-654https://www.ebi.ac.uk/biostudies/studies/S-EPMC11401469biostudies-literatureUnknown39(4)The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV)Virologica SinicaDesign of antiviral AGO2-dependent short hairpin RNAs.PMC114014692023YFC230590082172269U21A2042382222028Qiu YBie YZhang JChen JZhang YHuang MZhang LZhou XfalseDesign of antiviral AGO2-dependent short hairpin RNAs.The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV)2024-01-01T00:00:00Z2024 Aug2026-07-15T13:10:24.383Z2025-04-06T12:28:51.534ZS-EPMC114014693873418310.1016/j.virs.2024.05.001