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目的:运用虚拟筛选技术从传统中药数据库(traditional Chinese medicine database platform,TCMSP)中寻找HIV-1整合酶的中药小分子抑制剂。方法:以整合酶与细胞因子LEDGF/P75相互作用位点为靶点,运用分子对接技术进行首轮筛选,然后运用ADME/T预测进行第二轮筛选,最后基于靶点与药物相互作用位点进行第三轮筛选。结果:以原配体(4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)-methyl]-benzoic acid,D77)为阳性对照,筛选出2个类药性良好的天然小分子化合物,二者与HIV-1整合酶亲和力及相互作用基团均优于D77(新型的HIV-1整合酶抑制剂),并且确定了它们的中草药来源。结论:成功建立一整套高通量虚拟筛选HIV-1整合酶抑制剂的策略,该研究结果可促进从传统中药库中提取、设计以及实验合成新的抗艾滋病药物。
OBJECTIVE: To find a small molecule inhibitor of traditional Chinese medicine (HIV-1) integrase from traditional Chinese medicine database platform (TCMSP) using virtual screening technique. Methods: The integrase and LEDGF / P75 interaction site as a target, the use of molecular docking technology for the first round of screening, and then use the ADME / T prediction for the second round of screening, and finally based on the site of interaction with the drug site The third round of screening. Results: The recombinant lentiviral vector was constructed with the original ligand (methyl 4 - [(2,4-dioxo-3- (2-oxo-2-phenylethyl) -1,3-thiazolidin-5-ylidene] 2-ethoxyphenoxy) -methyl] -benzoic acid (D77) was used as positive control to screen out two natural small molecule compounds with good drug-drug properties. Both of them showed better affinity and interaction groups with HIV-1 integrase than D77 Of HIV-1 integrase inhibitors) and identified their source of herbal medicine. CONCLUSIONS: A successful strategy of high-throughput virtual screening of HIV-1 integrase inhibitors has been successfully established. The results of this study can facilitate the extraction, design and experimental synthesis of new anti-AIDS drugs from traditional Chinese medicine repositories.