金蒲桃中新型间苯三酚类成分抗RSV的构效关系和作用机制研究

Respiratory syncytial virus (RSV) infection seriously harms human life and health, but currently there are no safe and effective drugs to prevent and treat RSV infection. Fusion F protein, a transmembrane glycoprotein on the envelope of RSV, plays an important role in regulating the fusion of virus and host receptor. The small molecule fusion inhibitors acting on F protein can play an antiviral role in the early stage of infection, which is an important way and direction of the research of new anti-RSV drugs. In the previous study, we firstly found that some novel phloroglucinol-terpene adducts from Xanthostemon chrysanthus (Myrtaceae) showed significant anti-RSV activity. Moreover, we found that these components exert anti-RSV infection activity by inhibiting RSV-F protein. However, the structure-activity relationships and mechanisms of action of these active compounds are still worth further study. On the basis of the previous research work, this project intends to further systematically isolate and identify the phloroglucinol-terpene adducts of X. chrysanthus, and evaluate their ant-RSV activity. Otherwise, the structure-activity relationships and mechanism of action of these active compounds will also be studied. Our study will provide scientific basis for the research and development of new anti-RSV drugs.

呼吸道合胞病毒（RSV）感染严重危害人类生命健康，但目前尚无安全有效的疫苗和药物能防治RSV感染。融合F蛋白是RSV包膜上的跨膜糖蛋白，参与调控病毒与宿主受体融合的重要过程。作用于F蛋白的小分子融合抑制剂能够在感染早期发挥抗病毒作用，是新型抗RSV药物研究的重要途径和方向。我们在前期研究中首次发现来源于桃金娘科植物金蒲桃的新型间苯三酚杂萜类成分具有显著的抗RSV活性，并发现其通过抑制融合F蛋白而在病毒进入细胞的早期阶段发挥作用，但该类化合物的作用机制和构效关系尚有待深入探索。本项目拟在前期研究工作基础上，进一步分离富集金蒲桃中的间苯三酚杂萜类成分，评价它们对RSV的抑制活性并阐明其构效关系和作用机制，为研发新型抗RSV药物提供科学依据。

呼吸道合胞病毒（RSV）是世界范围内引发呼吸道感染的最常见的病原体，但目前尚无安全有效的药物能够治疗RSV感染。我们前期从桃金科黄蕊木属代表性植物金蒲桃中分离鉴定了结构新颖的间苯三酚类化合物，部分化合物显示出良好的抗RSV活性。项目在前期研究的基础上，进一步对金蒲桃中间苯三酚类成分进行系统分离和结构鉴定，构建了间苯三酚类化合物库，并研究了其抗RSV活性的构效关系和作用机制。从金蒲桃中共分离和鉴定了90个间苯三酚类化合物，其中40个为新骨架化合物。系统考察了不同结构类型的间苯三酚类化合物抗RSV活性的差异，发现间苯三酚-杂萜类化合物具有显著的抗RSV活性，其IC50优于或相当于阳性对照利巴韦林。作用机制研究结果表明，其作用靶点是病毒囊膜上的融合蛋白(RSV-F蛋白)。以上研究结果揭示了金蒲桃中的间苯三酚类化合物抗RSV的构效关系和作用机制，为寻找和开发出新的抗RSV药提供了先导化合物。