Yan Haiyan, Wang Huiqiang, Wang Kun, Wu Shuo, Jiang Jiandong, Li Yuhuan
CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int J Mol Sci. 2025 Jun 3;26(11):5358. doi: 10.3390/ijms26115358.
The influenza A virus (IAV) is a major cause of recurrent seasonal epidemics and global pandemics, posing a significant threat to public health. Although lycorine has demonstrated broad-spectrum antiviral activity, its specific mechanisms of action against IAV remain incompletely understood. In this study, we characterized the potent inhibitory effects of lycorine on seasonal and drug-resistant IAV subtypes (H1N1/H3N2) as well as the influenza B virus, showing its ability to suppress viral mRNA, viral titers, and M2 protein expression across multiple cell lines. Time-of-addition and time-course assays revealed that lycorine exerts multiphasic interference, and the critical late stage of the IAV life cycle aroused our interest to study this further. Mechanistically, we discovered that lycorine specifically interferes with the de novo synthesis of nucleoporin Nup93, thereby disrupting the nuclear export of viral nucleoprotein (NP). These findings not only establish lycorine as a promising broad-spectrum anti-influenza candidate but also provide new insights for developing host-targeted antiviral strategies.
甲型流感病毒（IAV）是季节性流行和全球大流行反复发生的主要原因，对公众健康构成重大威胁。尽管石蒜碱已显示出广谱抗病毒活性，但其针对IAV的具体作用机制仍未完全了解。在本研究中，我们表征了石蒜碱对季节性和耐药性IAV亚型（H1N1/H3N2）以及乙型流感病毒的强效抑制作用，显示出其在多种细胞系中抑制病毒mRNA、病毒滴度和M2蛋白表达的能力。添加时间和时间进程分析表明，石蒜碱发挥多阶段干扰作用，而IAV生命周期的关键后期引起了我们进一步研究的兴趣。从机制上讲，我们发现石蒜碱特异性干扰核孔蛋白Nup93的从头合成，从而破坏病毒核蛋白（NP）的核输出。这些发现不仅确立了石蒜碱作为一种有前景的广谱抗流感候选药物，还为开发针对宿主的抗病毒策略提供了新见解。
