传统中药蜘蛛香和广藿香中的抗达菲耐药流感病毒活性成分及其作用机制研究

流感是由流感病毒引起的严重威胁人类健康的急性呼吸道传染病。疫苗的滞后性和药物耐药性的出现，使得新型抗流感病毒药物在作用机制上亟待突破。病毒进入细胞环节, 因与突变频率低的宿主细胞识别，有望成为抗病毒药物研发的新契机。从疗效确切的传统中药中发现抗病毒活性成分，是开发抗病毒药物的重要途径。我们在前期工作中，从传统中药蜘蛛香和广藿香中发现了对达菲耐药流感病毒PR8具有显著抑制作用的广藿香醇型倍半萜和环烯醚萜。广藿香醇型倍半萜valeriananoid C的作用机制研究结果表明，其作用靶点可能是血凝素，该类成分有可能成为新的病毒进入抑制剂。本课题拟以抗达菲耐药流感病毒活性化合物的发现为导向，利用UPLC-Q-TOF-MS技术快速锁定目标化合物，对蜘蛛香和广藿香中的活性成分，即广藿香醇型倍半萜和环烯醚萜进行研究。作用机制研究重点考察活性化合物是否以血凝素为靶点，为开发新型流感病毒进入抑制剂奠定基础。

Influenza, an acute contagious respiratory disease caused by influenza viruses, represents one of the major threats to public health. The lagging of vaccines and the emergence of drug resistance leads to the urgent need for developing new anti-influenza viral drugs with novel mechanisms. The drugs which can prevent the entry of virus may be candidates of new kind of anti-influenza virus drugs. It is an important way to develop antiviral drugs from traditional Chinese medicine with definite curative effect.. In our previous work, three patchoulol-type sesquiterpenoids, valeriananoids A-C, along with three iridoids, jatamanvaltrate G, jatamanvaltrate H and chlorovaltrate J, isolated from Valeriana jatamansi, as well as a patchoulol-type sesquiterpenoids, (5R)-5-hydroxypatchoulol, isolated from Pogostemon cablin, showed potent anti-influenza virus activity against Tamiflu resistant influenza virus A/Puerto Rico/8/1934 (H1N1). Inhibition of PR8-HA-mediated hemolysis suggested that valeriananoid C inhibited influenza virus PR8 by targeting hemagglutinin and it could be a new inhibitor of viral entry. . In this study, guided by UPLC-QTOF-MS analysis and anti-Tamiflu resistant A virus assay, the active constituents in V. jatamansi and P. cablin, especially patchoulol-type sesquiterpenoids and iridoids, will be studied. As for active compounds, the mechanism study will mainly focus on the target of hemagglutinin, which will lay a foundation for the development of novel influenza virus entry inhibitors.