整合酶是Ⅰ型人类免疫缺陷病毒（HIV-Ⅰ）完整的生命周期不可或缺的催化酶之一。整合酶可以将逆转录酶产生的病毒DNA整合到宿主染色体中，从而帮助HIV-Ⅰ完成生活周期。以整合酶为靶点的抗艾滋病制剂的研究是最近几年来的热点。传统中草药具有结构多样性、低副作用的特点，已发现多种成分具有抗HIV活性，但是存在机制不清、靶点不明的缺点；迄今为止，完整的整合酶晶体结构或者整合酶与病毒DNA复合物的晶体结构仍然没有被解析。本研究通过同源模建构建处于链转移抑制状态的IN-vDNA-RAL复合物。然后利用该复合物产生基于受体-配体复合物的药效团模型。用产生的药效团模型对传统中草药数据库进行筛选，将筛选得到的化合物与构建的处于抑制状态的IN-vDNA复合物进行分子对接，得到11个结合自由能打分高于RAL药物的化合物。在这11个天然化合物中，2个化合物有实验数据证实具有体外抗HIV活性，另外9个属于新型的小分子，具有潜在的整合酶链转移抑制活性。; Integration of a DNA copy of the viral genome into a host cell chromosome is an essential step in the HIV-1 life cycle which is catalyzed by integrase. Integrase has been the promising target for developing the anti-AIDS agents.Traditional Chinese Medicines is characteristic of structural diversity and low side effects. Though some molecules identified from traditional Chinese medicines have anti-AIDS activity, the target and mechanism of action for those molecules remain unclear. So far, the structure information of full-length integrase, either vDNA-free or vDNA-bound, is not available. We constructed the IN-vDNA-RAL complex which remains RAL-inbitited by homology modeling. Guided by the complex model, we got a receptor-ligand based pharmacophore model and used the model to virtual screen the TCM datebase. After the filter of pharmacophore model, the remaining TCM compounds were docked to IN-vDNA complex which remain inhibited. Finally, we got 11 compounds whose binding ennery scores are better than RAL’s.Of the 11 compounds, 2 compounds had been identifid in the anti-AIDS activity experiments in vitro. The left 9 compunds are new molecules which has potential activity inhibiting the strand transfer reaction.
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