海洋真菌mf090产物Aurasperones 体外抗艾滋病病毒活性的研究.docVIP

  海洋真菌 mf090 产物 Aurasperones 体外抗 艾滋病病毒活性的研究# 游剑岚，刘广杰，陈志辉，秦莉，陈小平** 5 10 15 20 25 30 35 40 （中国科学院广州生物医药与健康研究院感染与免疫研究中心呼吸系统国家重点实验室，广 州 510530） 摘要：人免疫缺陷病毒（HIV）感染和艾滋病是人类健康和全球公共卫生的最重大挑战。目 前，临床上使用的药物无法彻底清除病毒，并且由于病毒的高效突变，病毒出现耐药是不可 避免的，因此需要急需研发新的药物。海洋真菌天然产物是新结构化合物的重要来源。本文 采用体外抗病毒实验从海洋微生物天然产物库中筛选出具有抗艾滋病毒的海洋真菌提取物， 并通过活性跟踪的方法分离出了具有抗艾滋病毒的活性物质 Aurasperone B 和 Aurasperone C，EC50 分别为 0.341 μM 和 1.43 μM，同时其细胞毒性 CC50 分别为 407 μM 和 161 μM 即 治 疗 指 数 高 达 1196 和 112.6 ， 具 有 良 好 的 应 用 前 景 。 进 一 步 采 用 不 同 时 点 加 药 （time-of-addition）方法，推测其作用靶点可能覆盖了病毒复制的早、中、晚期。 关键词：生物学；猴免疫缺陷病毒；海洋微生物天然产物; aurasperone; 抗 SIV 活性；HIV 中图分类号：R37 In Vitro Anti-HIV Activity of Aurasperones, Products of Marine Fungi mf090 You Jianlan, Liu Guangjie, Chen Zhihui, Qin Li, Chen Xiaoping (center for infection and immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences) Abstract: Human immunodeficiency virus (HIV) infection and AIDS are the most significant human health and the global public health challenges. Currently, the clinical drugs in use cannot completely eradicate the virus. Furthermore, it is inevitable that drug-resistant viruses occur easily because of the high mutation of HIV. Therefore the development of new anti-HIV drugs is urgently needed. Marine fungi natural products are important sources of new structure of compounds. We screened the extracts from a marine microbial natural products library by in vitro antivirus assays and tracked the components that had the antivirus activity. Two compounds, Aurasperone B and Aurasperone C, were isolated with high anti-SIV activity (EC50 0.341 μM and 1.43 μM respectively), low cytotoxicity (CC50 407 μM and 161 μM respectively) and high therapeutic index up to 1196 and 112.6 respectively, which showed good prospects. By using time-of-addition assay, we speculated that the anti-virus target probably covered the early, middle and late stage of the viral replication cycle. Key words: microbiology; Simian immunodeficiency virus; marine micr