临床抗乙肝病毒（HBV）药物结构类型单一，面临毒性强、耐药性明显的问题。高效识别，快速寻找和衍生结构多样化的天然抗乙肝病毒活性分子，是抗HBV药物研究的重要方向之一。我们前期首次发现结构新颖的没药烷型倍半萜显示选择性抗乙肝病毒活性，初步构效关系研究发现多个活化位点可以增加没药烷型倍半萜抗乙肝病毒的SI值。在此基础上，本项研究拟继续从叶下珠属植物西印度醋栗中富集反应底物pyllanthusol A，分离结构多样新颖的没药烷倍半萜，同时以pyllanthusol A为底物，对活性位点进行结构修饰。采用瞬时耐药质粒转染及靶向机制相结合的方法，进一步挖掘和丰富抗HBV没药烷型倍半萜活性分子，探讨没药烷型倍半萜分子抗HBV构效关系。并从Hsc70蛋白、TOLL-like受体等抗HBV新靶点多方面探讨其作用机制，以期发现新的抗HBV先导分子，为抗HBV药物的开发提供科学基础。

Anti-HBV Drugs face a serious challenge caused by toxicity, resistance and limited chemical scaffolds. An important research strategy in antiviral discovery is to investigate the diverse active natural products by isolation and synthesis. Previously, we isolated some new oxygenated bisabolane sesquiterpenoid glycosides.Most of them exhibited potential anti-HBV activity. The proposed research in this project will continue our investigation on P. acidus to yield the reaction substrates and various bisabolanes. Furthermore, structural modification will be done in the active site of pyllanthusol A. Using genetically-modified viral strains, as well as a variety of target enzymes, the possible antiviral mechanisms of the active compounds will be investigated. Our goal is to identify a couple of anti-HBV lead compounds, laying a foundation for developing new and safer antiviral drugs.