深海来源真菌中靶向病毒血凝素蛋白的抗甲型流感活性成分发现和优化

甲型流感病毒造成了多次全球范围的流感蔓延，具有巨大的社会危害性。流感病毒的血凝素蛋白（HA）是病毒包膜上的糖蛋白，在流感病毒的侵染和复制过程中发挥着重要作用，是目前最受关注的抗流感药物靶点之一。深海真菌生存环境独特，作为具有庞大基因组和复杂代谢机制的真核微生物，能够编码产生结构新颖的活性次级代谢产物，有可能进化产生独特的抗病毒成分。本研究在前期基础上，以病毒的HA蛋白为靶标，聚焦深海来源真菌开展新型抗流感药物先导化合物的发现和优化研究：寻找深海来源真菌中具有抗甲型流感病毒作用的活性成分；并阐明活性化合物（如HDYL-18）与HA蛋白的相互作用模式、探讨其构效关系，并进行结构优化；以期获得高效、低毒的新型抗流感活性化合物，为海洋创新药物研究奠定基础。

Influenza A virus (IAV) causes seasonal influenza epidemics resulting in high mortality and morbidity, and makes a threat to public health and global economy. As a type of envelope glycoprotein in IAV, hemagglutinin (HA) plays a critical role in viral binding, fusion and entry. HA becomes one of the most appealing target for developing anti-IAV drugs. Deep-sea derived fungi are eukaryotic microorganism with huge genome and complicated metabolic mechanism, leading to the production of molecules with structural novelty and diverse bioactivity. Surviving in the specific deep sea environment, deep-sea derived fungi maybe evaluate unique secondary metabolites with anti-viral activity. In this research, we will explore new anti-influenza virus molecules targeting HA from the secondary metabolites of deep-sea derived fungi, and elucidate the mode of action of the potential active compounds, as well as optimize the structure of a previous disclosed active compound HDYL-18 with the study of its structure-activity relationship. Supported by this project, we hope to find our new marine drug leads for therapy influenza.