“shock and kill”是通过“shock”药物激活潜伏HIV病毒，而后用“kill”药物（高效抗逆转录病毒疗法）清除激活的病毒，达到根除HIV的目的，是目前国际上抗AIDS研究的热点。其关键在于如何从天然产物中寻找发现HIV潜伏激活的活性成分，这也是当前抗AIDS药物研发的重点。前期，申请人选取中国海洋微生物菌株保藏管理中心所有的104株深海链霉菌，通过HIV潜伏激活活性测试及成分分析，发现1A09851和1A01793不仅次级代谢产物丰富，而且具有很强的活性（在10 μg/mL浓度下，其激活率分别为23.7%和21.1%，约为阳性对照药的50%）。因此本项目拟以该两株深海链霉菌为研究对象，以活性为导向，发现HIV潜伏激活的活性成分，对活性最好的目标化合物进行大量富集，深入研究其作用机制。通过本项目研究，有望为具有我国完全自主知识产权的抗AIDS药物的研发提供模式结构和药物前体。

The “shock and kill” strategy works by two steps: the first “shock” step by giving a drug revives latent HIV in patients; then the second “kill” step to clear all activated HIV by Highly Active Antiretroviral Therapy (HAART). Since HAART is universally recognized as one of the most effective approach to treat AIDS, the key point of the strategy is to discover compounds from natural sources with latent HIV reactivation bioactivities, which is also the hotspot for research and development of the anti-AIDS drugs. On the basis of huge microorgamisn resources of the Marine Culture Collection of China (MCCC), all 104 deep-sea derived streptomycetes in MCCCC were selected and subjected to small-scale fermentation. Their crude extracts were tested for HIV latency reactivative activities and analysed for chemical compositions as well. Consequently, two strains of streptomyces sp. 1A09851 and 1A01793 were found to have diverse components and potent bioactivities (The reactivation rates were 23.7% and 21.1%, respectively, under the concentration of 10 μg/mL, which was about 50% compared to that of the positive control). Therefore, these two strains were chosen in this project to search for HIV latency reactivative compounds using bio-guided isolation. The most bioactive compounds will be accumulated by 100 L large-scale fermentation under optimized media and conditions. Then it will be subjected to in-depth bioactive mechanism study. In general, the project will afford some anti-AIDS lead compounds with the self-property right completely owned by our country.