病毒的寄生性，使开发高选择性的抗病毒药物存在极大困难。前期通过活性跟踪，从苦木科植物鸦胆子中发现一系列具有显著抗烟草花叶病毒(TMV) 活性的C-20型苦木素类化合物，其中活性最强的brusatol活性相当于阳性对照药宁南霉素的34倍。研究表明此类化合物不仅能抑制病毒的侵染、复制，而且在先施药的情况下可显著减轻烟草感染TMV的发病症状，化合物是否能激发植物的抗病性？苦木素能否作为新型的化学激活剂？鉴于苦木素类化合物结构复杂多变，很可能存在更多的抗TMV活性苦木素。本研究将在前期研究的基础上，继续运用现代分离纯化技术和结构鉴定手段，从锁定的活性部位，分离富集苦木素类化合物，研究其结构和活性特点，分析构效关系，并结合生物化学和分子生物学手段进一步研究苦木素类化合物的抗病毒机理，从中寻找高效、低毒的天然抗病毒先导化合物，为新型植物病毒抑制剂的研究提供科学依据。

It was difficult to develop safe and effective antiviral drugs because viruses use the host's cells to replicate，and now the great breakthrough in this research field is still blank. Previously we found a series of C-20 type qussinoids from Brucea javanica with potent antiviral activity against tobacco mosaic virus (TMV) according to bioassay-guided isolation. The most active brusatol was equivalent to 34 times the activity of ningnanmycin, a positive control antiviral drug. However, the antiviral mechanism of quassinoid was unknown. According to our present research, quassinoids from B. javanica could not only inhibit the accumulation of TMV CP, but also enhance the host plant’s resistance to TMV infection. Whether quassinoids could improve the disease resistance of plant and be conducted as new chemical activator? Considering the diversity of quassinoids, in this project, we will continue isolating the active quassinoids responsible for the anti-TMV activity by methods of modern purification and structure-identification techniques. In addition, we will analyze the structure-activity relationship of the active compounds. In order to seek for effective antiviral lead compounds with high activity and low toxicity, we will further study the antiviral mechanisms of those active quassinoids from B. javanica by methods of biochemistry and molecular biology. Those works will provide bases for further exploration of new plant virus inhibitors.