三株西沙海绵来源真菌中抗手足口病致病病毒EV71活性代谢产物的发现

项目名称： 三株西沙海绵来源真菌中抗手足口病致病病毒EV71活性代谢产物的发现

项目编号： No.21502204

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 环境科学、安全科学

项目作者： 王俊锋

作者单位： 中国科学院南海海洋研究所

项目金额： 21万元

中文摘要： 由肠道病毒(EV71)引发手足口病(HFMD)的全球大流行严重威胁到人类尤其是儿童的健康。HFMD至今尚无有效药物和安全疫苗可用。研发结构新颖、活性显著的抗EV71药物刻不容缓。目前国内外学术界对微生物来源的抗EV71活性成分研究却罕见报道。因此，申请者系统筛选了21株分离自西沙海绵真菌发酵产物的抗EV71活性，并进一步从中首次发现抑制活性与Ribavirin相当的抗EV71活性生物碱Arthpyrone D，前期研究成果开拓了抗EV71先导化合物发现的新来源，提供了近年来预防HFMD的新思路。本项目以抗EV71活性为导向，运用化学和光谱学方法，拟从三株前期筛选具有显著抗病毒活性的海绵真菌中快速分离并结构确定抗EV71活性的化学分子，优化发酵条件，富集活性代谢产物，发现、衍生新的抗EV71先导结构，揭示其构效关系，探明其潜在的药效基团，为研制真菌来源的新型抗病毒药物提供科学依据和物质基础。

中文关键词： 海绵来源；真菌；次生代谢产物；抗肠道病毒活性；构效关系

英文摘要： In recent years, the hand, food and mouth disease (HFMD) is an acute infectious disease caused by enterovirus family, in which enterovirus 71 (EV71) is the most common pathogen. This diease spreads through a variety of ways, and occurs all around the world. Pre-school children especially children aged 5 years and below have the highest disease incidence. Serious cases could lead to neurological symptoms and even death. Currently, clinically effective antivirals for use in the treatment of enteroviral infection do not exist. Thus, there is a tremendous clinical need to develop novel classes of antiviral agents for the treatment of enterovirus infection. Marine microorganisms with a high degree of species diversity can produce structurally novel secondary metabolites, which are an important resource for discovery of new leading compounds. Our aim was to identify antiviral metabolites from sponge-derived fungi. Twenty-one strains of marine fungi were isolated from the marine sponge, Phakellia fusca Thiele, collected from the Xisha Islands of China. The previous research has screened the effective extracts of different fermentation broth of sponge-derived fungi for treating the EV71 and for the first time to separate five 4-hydroxy-2-pyridone alkaloids, in which there are four new compounds. At the same time, arthpyrone D could significantly inhibit EV71 virus multiplication on Vero cells. Optimizations of fermentation condition for these strains were systematically studied. This research is on multi-discipling cooperation of marine biology, microbiology, and marine natural products. Guided by antiviral activity against the enterovirus 71, we will investigate the chemical components from the secondary metabolites of three sponge-derived fungi. Furthermore, we will study structure-activity relationships for some of the more promising compounds, and optimize the lead compounds. Above studies would provid theoretical basis to further research for obtaining antiviral agents from marine fungi.

英文关键词： sponge-derived ;fungi;secondary metabolite;anti-EV71 activity;SAR