基于多靶点分子对接初探宣肺化浊方治疗新型冠状病毒肺炎的物质基础  

Material Basis of Xuanfei Huazhuo Prescription in Treatment of COVID-19 by Multi-target Molecular Docking

作　　者：冯彩琴 张志明 张月梅[3] 王燕如 雍文兴 台安宁 李丹桂 靳晓杰 刘永琦 FENG Cai-qin;ZHANG Zhi-ming;ZHANG Yue-mei;WANG Yan-ru;YONG Wen-xing;TAI An-ning;LI Dan-gui;JIN Xiao-jie;LIU Yong-qi(Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China;Dunhuang Key Laboratory of Medicine and Transformation under Ministry of Education,Gansu Provincial Key Laboratory for Molecular Medicine of Major Diseases and Prevention and Treatment with Traditional Chinese Medicine for Colleges and Universities,Gansu University of Chinese Medicine,Lanzhou 730000,China;The First Hospital of Lanzhou University,Lanzhou 130000,China)

机构地区：[1]甘肃中医药大学附属医院,兰州730000 [2]甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,敦煌医学与转化省部共建教育部重点实验室,兰州730000 [3]兰州大学第一医院,兰州730000

出　　处：《中国实验方剂学杂志》2020年第16期32-39,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：甘肃省高校重大疾病分子医学与中医药防治研究重点实验室新型冠状病毒防治科研专项开放基金项目(FZYX20-3)。

摘　　要：目的:运用分子对接、靶点反向预测及反向分子对接技术探索宣肺化浊方治疗新型冠状病毒肺炎(COVID-19)的物质基础及可能的分子机制。方法:在中药系统药理学分析平台(TCMSP)检索宣肺化浊方中10味中药化合物,以血管紧张素转换酶2(ACE2),白细胞介素-6受体(IL-6R)为靶蛋白,运用分子对接筛选方中与ACE2,IL-6R对接打分较好且符合类药性的化合物,并进行化学信息学层次聚类分析;利用Swiss Target Prediction预测化合物潜在靶点;运用Cytoscape构建化合物-靶点网络;利用STRING分析靶点蛋白互相作用。结果:宣肺化浊方中针对ACE2潜在有活性的化合物共312个,活性较强的化合物15个;针对IL-6R符合条件的活性化合物共100个,活性较强的化合物3个,对活性较强的化合物进行化学信息学层次聚类分析发现大多属于黄酮类。药味-有效成分-靶点网络包含药材10味、化合物126个、靶点130个;STRING分析显示磷脂酰肌醇3激酶调节亚基1(PIK3R1),肉瘤基因(SRC),丝苏氨酸蛋白激酶1(AKT1),雄激素受体(AR)和表皮生长因子受体(EGFR)等蛋白可能是宣肺化浊方起效的关键靶点。结论:本研究基于多靶点分子对接虚拟筛选初步得到宣肺化浊方抗病毒、抗炎的物质基础,同时结合靶点反向预测和分析探索该方治疗COVID-19潜在作用靶点和分子机制,为宣肺化浊方及其相关方药的多角度挖掘和单体成分的现代化开发提供线索。Objective: Structure-based angiotension converting enzyme 2(ACE2)and interleukin-6 R(IL-6 R)were taken as the target proteins to in the investigation of the material basis of Xuanfei Huazhuo prescription in the treatment of coronavirus disease-2019(COVID-19)by molecular docking. Method: The compounds in Xuanfei Huazhuo prescription were retrieved through TCMSP. Structure-based ACE2 and IL-6 R were taken as the target proteins to screen out the compounds with a better activity by molecular docking,and analyze structural properties of these compounds. Furthermore,the potential molecular mechanism of Xuanfei Huazhuo prescription in the treatment of COVID-19 was analyzed by target reverse prediction. Result: There were 312 potentially active compounds in Xuanfei Huazhuo prescription,including 75 highly active compounds and 15 highly active compounds for ACE2. There were 100 eligible active compounds and 3 highly active compounds for IL-6 R,most of which belong to flavonoids. The herb-component-target network included 10 herbs,126 compounds and 130 targets. String analysis showed that PIK3 R1,SRC,AKT1,AR and EGFR might be the key targets of Xuanfei Huazhuo prescription. Conclusion: Based on the virtual screening of multitarget molecular docking,the anti-virus and anti-inflammatory material basis of Xuanfei Huazhuo prescription was preliminarily obtained. At the same time,based on the reverse prediction and analysis,potential targets and molecular mechanism of the recipe in the treatment of COVID-19 were explored,so as to provide clues for the multi-angle mining of Xuanfei Huazhuo prescription and its relevant prescriptions and the modernization development of monomer components.

关 键 词：新型冠状病毒肺炎(COVID-19) 宣肺化浊方 血管紧张素转换酶2(ACE2) 白细胞介素-6受体(IL-6R) 分子对接 

分 类 号：R2-0[医药卫生—中医学] R22