高致病性流感严重威胁人类的生命健康，而防治流感的药物仍十分有限，研制开发新型抗流感药物已刻不容缓。流感病毒的复制依赖于特定的宿主蛋白，作用于宿主蛋白的流感病毒抑制剂具有抗病毒谱广、避免病毒耐药、候选靶点丰富等诸多优势，因此，以宿主蛋白为靶标已成为当前抗流感药物研发的新策略。我们在前期工作中，首次发现石蒜碱型化合物对多种流感病毒具有显著抑制作用，初步的作用机制研究表明，石蒜碱能显著抑制流感病毒RNP复合物的出核转运，并通过作用于宿主蛋白而发挥作用，这不同于现有抗流感药物的作用机制。本项目拟在前期工作基础上，进一步对石蒜碱类成分进行分离和鉴定，并对石蒜碱进行结构修饰，以构建类天然产物库，在此基础上研究石蒜碱类化合物抑制流感病毒RNP出核转运的作用机制和构效关系，为寻找和发现高效广谱的抗流感药物提供科学依据。

Frequent outbreaks of highly pathogenic influenza and the continuous variation of IFV have made a serious threat to human health. Influenza virus replication relies on the expression of the host protein in infected cells. Influenza virus inhibitors that target the host protein have many advantages, such as broad anti-viral spectrum, low drug-resistant and rich candidate target. Thus, targeting to host protein is a new strategy for anti-IFV drug development. In the previous work, we found lycorine analogues significantly inhibited the replication of various influenza viruses for the first time. Preliminary mechanism studies have shown that although lycorine has no effect on the viral proteins, it could significantly inhibit the nuclear-to-cytoplasmic export of ribonucleoprotein (RNP) complex and act on the host proteins. This machnism is differernt from available clinical drugs. This project is based on the previous work and to build a library of natural product analogues by further isolation of lycorine type compounds and structure modification of lycorine. In addition, this project will study the anti-IFV activity, mechanism of action and structure-activity relationship of lycorine analogues, which will provide a scientific information for the development of anti-IFV drugs with highly effect and broad spectrum.