丙型肝炎是由丙型肝炎病毒(HCV)引起的一种严重威胁人类健康的疾病。近年来直接抗病毒药物(DAAs)的快速发展使丙型肝炎的治愈率大大提高，但DAAs都为核苷类化合物，存在一定的副作用且价格高昂。中医药在肝炎等疾病防治中发挥着重要作用，且源于中药的天然产物具有结构多样性、低毒等特点，故中药是寻找新的抗HCV先导化合物的重要源泉。前期的研究工作发现金粟兰属植物银线草中的倍半萜二聚体具有显著抗HCV活性，其中化合物1的体外活性(EC50=1.62 μM) 是临床治疗HCV用药利巴韦林的近30倍。为了得到结构多样性的抗HCV倍半萜低聚物，本项目拟对富含倍半萜低聚物的金粟兰属两种植物开展定向分离，高含量成分的转化与结构修饰，开展其抗HCV构效关系研究，阐明该类低聚物抗HCV活性的必要骨架和基团，为后续结构优化提供依据，并对其作用机制进行研究，为今后优选出抗HCV新药候选分子奠定科学基础。

Hepatitis C, caused by the hepatitis C virus (HCV), is a seriously global problem of human health. In recent years, nucleoside analogues (such as DAAs), as the most used anti-HCV drugs, play an important role in the therapy of hepatitis C. Although the new direct antiviral agents (DAAs) have greatly improved the cure rate of hepatitis C, DAAs are drugs with short period of clinical use, side effects, and high price. Traditional Chinese Medicine (TCM) plays an important role to the treatment of hepatitis C and other diseases in China. Natural products (NPs) obtained from TCM act as a main resource of finding new anti-HCV leading compounds. In our previous study of discovering anti-HCV constituents from TCM, we find out that the lindenane-type disesquiterpenoids from Chloranthus plants showed significant anti-HCV activity for the first time. In vitro, the anti-HCV activity of compound 1 (EC50=1.62 μM) is nearly 30 times better than that of Ribavirin, which is one of the best clinical drug used to treat hepatitis C. In order to discover more structurally diverse analogues of compound 1, this project will carry out the study of the structure-oriented isolation of sesquiterpenoid oligomers from two plants of the genus Chloranthus and structural modification. Furthermore, we will research the structure-activity relationship (SAR), elucidate the indispensable skeleton and pharmacophore of anti-HCV activity, study their preliminary mechanisms, and lay the foundation of finding more new anti-HCV candidate molecules.