中药化学数据库中HIVRT(NNRTI)/IN双靶点抑制剂的虚拟筛选  

Virtual screening of double target inhibitor of RT(NNRTI)/IN against HIV from traditional Chinese medicine database

作　　者：肖泽云[1] 李凯[1,2] 李爱秀 XIAO Zeyun;LI Kai;LI Aixiu(Drug Design Laboratory of the Basic Science Department, Logistics University of PAP, Tianjin 300309, China;PharmacyDepartment, Shanxi General Hospital of PAP, Taiyuan 030006, China;Tianjin Key Laboratory for Prevention and Control ofOccupational and Environmental Hazard, Tianjin 300309, China)

机构地区：[1]武警后勤学院基础部药物设计实验室,天津300309 [2]武警山西总队医院药剂科,太原030006 [3]天津市职业与环境危害防制重点实验室,天津300309

出　　处：《天津中医药》2018年第5期386-391,共6页Tianjin Journal of Traditional Chinese Medicine

基　　金：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)

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。[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.

关 键 词：天然产物 逆转录酶 整合酶 双靶点抑制剂 虚拟筛选 

分 类 号：R2-03[医药卫生—中医学]