流感病毒是临床上危害性最大的呼吸道感染病原体，因其外膜蛋白的易变异和药物的耐药性等问题，现有的手段已不能有效地防治流感的暴发和流行。流感病毒核糖核蛋白（RNP）出核是病毒复制中的重要环节，寻找RNP出核抑制剂已成为当下研究抗流感病毒新药的热点。我们的前期研究结果显示，鹅不食草的CO2超临界萃取物中部分伪愈创木烷型倍半萜内酯具有很好的抗流感病毒活性，某些化合物的活性高于阳性对照药利巴韦林，而且初步的构效关系分析显示其活性基团和毒性基团有所区别。在作用机制的研究中，我们首次发现鹅不食草伪愈创木烷型倍半萜内酯作用于流感病毒复制晚期，可抑制病毒RNP出核。故本项目拟在前期研究的基础上，进一步对鹅不食草中倍半萜内酯类化合物进行分离和结构鉴定，评价该类化合物抗病毒活性，深入探讨其构效关系，并对其抑制流感病毒RNP出核的作用机制及可能的作用靶点进行深入研究，为研究和开发新型的流感病毒药物提供科学依据。

Influenza virus is the most harmful respiratory pathogen in clinical. Due to the high mutation rate of the virus and the high levels of drug resistance, the current preventive and therapeutic strategy couldn’t be effective to control the outbreaks and pandemics of influenza virus. The nuclear export of RNP is an important process during influenza replication cycle, and looking for inhibitors which act on the nuclear export of influenza RNP from infected cells is becoming a research hotspot for the development of new anti-influenza virus drugs. Our previous study showed that some pseudoguaianolides from the supercritical fluid extract (SFE) of Centipeda minima exhibited excellent anti-influenza virus activity, several of them possessed more potent antiviral activity than ribavirin (positive drug); furthermore, the preliminary structure-activity relationship (SAR) analysis indicated that their active moiety and toxic moiety are different. In mechanistic study, we firstly found that pseudoguaianolides influenced the late stage of influenza virus life cycle and inhibited the nuclear export of viral RNP. On the basis of our previous work, the project will be conducted to further isolate and identify the sesquiterpene lactones from SFE of C. minima and evaluate their anti-influenza virus activity, and then to study their SAR and mechanism of the sesquiterpene lactones against viral RNP nuclear export. The present study will provide the scientific support for developing new drugs in the treatment of influenza infection.