| 摘要: |
| [目的] 从天然产物中筛选人类免疫缺陷病毒（HIV）非核苷类逆转录酶抑制剂（NNRTI）和整合酶链转移抑制剂（INSTI）作用位点的双靶点抑制剂[RT （NNRTI）/IN]。[方法] 运用分子模拟技术和计算机辅助药物设计（CADD）方法，构建HIV RT （NNRTI）/IN双靶点抑制剂分子相似性搜索模型、NNRTI和RT以及INSTI和IN对接模型，采用两种策略对中药化学数据库（TCMD）进行筛选。[结果] 共命中与RT和IN对接得分均大于6的化合物35个，包括黄酮类、生物碱类、苷类、多酚类等，黄酮类化合物（15个）占到了42.86%。[结论] 黄酮类化合物是开发潜在HIV RT （NNRTI）/IN双靶点抑制剂的主要来源，上述研究为天然产物来源的HIV双靶点药物发现提供了新线索。 |
| 关键词: 天然产物 逆转录酶 整合酶 双靶点抑制剂 虚拟筛选 |
| DOI：10.11656/j.issn.1672-1519.2018.05.16 |
| 分类号:R2-03 |
| 基金项目:国家自然科学基金项目（81241114，30472166）；天津市科技攻关计划重点科技攻关专项基金资助项目（06YFGZSH07000）；武警后勤学院研究生创新课题（WHYC201610，WHYC201605）。 |
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| Virtual screening of double target inhibitor of RT(NNRTI)/IN against HIV from traditional Chinese medicine database |
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XIAO Zeyun1, LI Kai1,2, LI Aixiu1,3
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1.Drug Design Laboratory of the Basic Science Department, Logistics University of PAP, Tianjin 300309, China;2.Pharmacy Department, Shanxi General Hospital of PAP, Taiyuan 030006, China;3.Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin 300309, China
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| Abstract: |
| [Objective] To find double target inhibitor of RT(NNRTI)/IN against HIV from natural products.[Methods] Molecular simulation and CADD technologies were used to build molecular similarity search model of double target inhibitor of RT(NNRTI)/IN against HIV, docking model of NNRTI and RT, docking model of INSTI and IN. Two strategies were used to screen Traditional Chinese Medicine Database(TCMD).[Results] The 35 molecules which docking scores with RT and IN were both above 6 were hit. There were flavonoids, alkaloids, glycosides, polyphenols, etc. Flavonoids(15) accounted for 42.86%.[Conclusion] Flavonoids are the main sources for the development of potential double target inhibitor of RT(NNRTI)/IN against HIV. These results provide new clues for the study of the dual target drugs of HIV derived from natural products. |
| Key words: natural product reverse transcriptase integrase double target inhibitor virtual screening |
