流感是历史上死亡人数最多的呼吸道传染病，目前临床上尚无理想的抗流感药物，因此新型抗流感药物的研发迫在眉睫。从深海真菌中寻找结构奇特、机制新颖的活性成分是当前抗流感药物研发的重要方向。前期申请人对大西洋深海热液区硫化物来源的86株真菌进行了流感活性测试及UPLC-DAD化学分析，发现Aspergillus sp.XT20、Graphostroma sp.XW42和Acremonium sp.XW19等3株真菌代谢产物丰富且活性较好。因此本项目拟以该3株深海真菌为研究对象，以活性和化学为评价指标进行发酵条件优化及大规模培养；进而以活性为导向，采用现代色谱分离方法从发酵产物中分离抗流感活性成分；然后利用NMR等理化数据鉴定结构并对其进行构效关系探讨。通过本项目的研究，可填补Graphostroma属真菌化学研究空白，并获得一批抗流感活性化合物，有望为新型抗流感药物的研发提供海洋来源的先导化合物。

Influenza virus are major human pathogens that cause the most deaths in respiratory diseases. However, there are no ideal anti-influenza drugs in clinic because of the high drug-resistant influenza virus. Thus, it is urgent to discover new anti-influenza drugs. Currently, to explore anti-influenza bioactive compounds from deep-sea fungi is a hot spot for discovery anti-influenza drugs. Previously, eighty six fungi were isolated from deep-sea sulphide ore deposits of the Atlantic. The cultured extracts of the eighty six fungi were subjected to anti-H1N1 bioassay and further to UPLC-DAD analysis. As a result, three fungi of Aspergillus sp.XT20、Graphostroma sp.XW42 and Acremonium sp.XW19 were found with potent bioactivities and diverse chemical components. Therefore, they were selected in this project for further investigation. In brief, fermentation optimization and large-scale cultivation will be carried out according to bioactivity and chemical analysis of the culture extracts. Then, anti-influenza bioactive compounds will be obtained from crude extracts using bio-guided isolation and their structures will be determined mainly by detailed analysis of NMR data and HRESIMS spectroscopic data. Finally, all compounds will be evaluated for their anti-influenza virus activities and structure-activity relationships will be preliminary discussed. This project will give the first report on chemical constitutions of the fungal genus Graphostroma. In addition to, it will be expected to provide drug precursors and model structures for the discovery and development marine-derived anti-influenza drugs.