基于片段的药物设计(FBDD)是药物设计和发现的新方法，其通过片段融合拼接，能高效发现药物尺寸合适且能作用于靶标蛋白多个亚活性腔的候选药物。研究提示天然存在的聚/杂合倍半萜的活性或选择性均优于单分子倍半萜。在生物体酶的作用下，骨架类型非常丰富且分子量在250D左右的单分子倍半萜可作为有效片段，被融合拼接，形成了一系列天然存在的符合FBDD理念的聚/杂合倍半萜。据此，我们提出了基于天然片段药物设计(NFBDD)的科学假设。云木香是菊科风毛菊属植物，前期研究提示云木香富含抗乙肝病毒（HBV）的单分子倍半萜。我们的研究提示云木香中除单分子倍半萜外，还具有结构新颖的聚/杂合倍半萜。本项目拟基于NFBDD的科学假设，在前期基础上，分离鉴定云木香中结构新颖的聚/杂合倍半萜；并以高含量的单分子倍半萜为前体，模拟合成聚/杂合倍半萜，测试抗HBV活性，发现先导分子，为天然药物的研究提供新思路。

Fragment-based drug design (FBDD) is a novel tool for drug discovery, which combined fragments to develop new lead compounds with fit drug size and acting on protein targets effectively. FBDD method has improved the progression from new medicines to the clinic. Previous studies suggested that poly/hybrid sesquiterpenoids showed better activity and higher selectivity than that of sesquiterpenoids. The natural sesquiterpenoids were excellent fragments, which are used as precursors to synthesize diverse poly/hybrid sesquiterpenoids by enzyme in plants. Therefore, we propose the hypothesis of natural fragment-based drug design (NFBDD). Aucklandia lappa Decne. (Saussurea lappa Clarke) belongs to Compositae family and its dry root is the medicinal herbs at Yunnan province. Previous studies showed that the root of S. lappa is rich in anti-HBV sesquiterpenoids. Our previous research suggested that novel diverse poly/hybrid sesquiterpenes might be found in S. lappa except for sesquiterpenoids. Therefore, based on the scientific hypothesis of NFBDD, we will continue to isolate the novel poly/hybrid sesquiterpenes from the root of S. lappa and use sesquiterpenoids being rich in S. lappa to synthase the dimer sesquiterpenoids and amino acid hybrid sesquiterpenoids. The structure-activity relation of all the anti-HBV compounds will be studied in order to find the novel anti-HBV lead compound.