福建农业学报2026，Vol.41Issue(5)：567-575,9.DOI:10.19303/j.issn.1008-0384.2026.05.006
β-d-N4-羟基胞苷抑制流感病毒复制并诱导基因组突变
Mutagenic Effect of β-d-N4-hydroxycytidine in Inhibiting Influenza A Virus Replication
摘要
Abstract
[Objective]Mechanism of β-d-N4-hydroxycytidine[HNC(EIDD-1931)]of Molnupiravir[Mol(EIDD-2801)]in inhibiting the highly mutable influenza A virus(IAV),which resisted to drugs and rendered vaccination ineffective,was investigated.[Method]A549 cells were infected with A/Puerto Rico/8/1934(H1N1)and treated with NHC in varied concentrations.RNA replication,protein expression,and progeny virus particle release of the virus were determined by qRT-PCR,Western blot,and plaque assay.Molnupiravir,the precursor drug of NHC,were administered to mice.Body weight,survival rate,lung tissue viral load,inflammatory factor expression,and pathological damage on the control and treatment mice were compared,and genome mutations of the virus sequenced.[Results]It was proved that NHC could inhibit viral nucleic acid replication and protein expression in vitro in a dose-dependent manner.In vivo,its prodrug,Molnupiravir,could significantly inhibit viral load and inflammatory factor expression in mouse lungs and alleviate lung injury in mice.The genome mutations on the virus were mainly manifested as A-G and U-C transitions.[Conclusion]NHC in Mol was highly effective against IAV.The accumulated specific mutations in genome induced by NHC contributed to the antiviral effect as observed,suggesting plausible application of the nucleoside analogue for combating the difficult virus.关键词
A型流感病毒/β-d-N4-羟基胞苷/核苷类似物/抗病毒药物/莫诺拉韦Key words
influenza A virus/β-d-N4-hydroxycytidine/nucleoside analogues/antiviral drug/Molnupiravir分类
医药卫生引用本文复制引用
刘倩芸,马晓霞,蓝秋菊,安乐乐,刘俊林..β-d-N4-羟基胞苷抑制流感病毒复制并诱导基因组突变[J].福建农业学报,2026,41(5):567-575,9.基金项目
甘肃省自然科学基金项目(23JRRA715) （23JRRA715）
