银翘散中抗流感病毒成分与神经氨酸酶的分子对接研究  

Study on the Molecular Docking of Anti-influenza Virus Components in Yinqiao Powder and Neuraminidase

作　　者：郭小华[1] 朱燕亮 程齐来[1] GUO Xiaohua;ZHU Yanliang;CHENG Qilai(College of Pharmacy,Gannan Medical College,Jiangxi Ganzhou 341000,China;Dept.of Pharmacy,Jiangxi Province Shangyou Hospital of TCM,Jiangxi Ganzhou 341200,China)

机构地区：[1]赣南医学院药学院,江西赣州341000 [2]江西省上犹县中医院药剂科,江西赣州341200

出　　处：《中国药房》2018年第17期2351-2355,共5页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81360627);江西省教育厅科学技术研究项目(No.GJJ161002);赣南医学院科研课题(No.YB201426)

摘　　要：目的:研究银翘散中17个主要抗流感病毒成分与神经氨酸酶(NA)的结合模式和相互作用。方法:采用CORINA、UCSF Chimera 1.3、Auto Dock Tools 1.5.4等分子对接软件,将银翘散中的甘草素、甘草苷、绿原酸、3,3′,4-三甲氧基鞣花酸等17个活性成分及阳性对照扎那米韦的二维结构转化成三维结构,确立其空间坐标,再设置受体蛋白NA的网格,并运行对接程序进行对接运算。以估计抑制常数(Ki)和结合自由能(ΔGbind)为参考指标,比较对接分子的虚拟活性差异,并从对接构象上分析产生活性差异的原因。结果:在17个活性成分中,绿原酸对接的Ki值为1.20μmol/L,ΔGbind值为-8.08 kcal/mol(1 kcal=4.184 k J),优于扎那米韦(Ki值为2.26μmol/L,ΔGbind值为-7.70 kcal/mol);3,3′,4-三甲氧基鞣花酸对接数据最差,Ki值和ΔGbind值分别为149.41μmol/L、-5.22 kcal/mol。在对接构象上,绿原酸与扎那米韦相似,在空间上更加匹配NA活性腔的活性位点,占据了除S5以外的所有活性位点,呈现出与NA较强的结合作用。3,3′,4-三甲氧基鞣花酸的平面分子结构限制了其与NA多个活性位点结合,对接构象不牢固。结论:绿原酸可能是银翘散中最强的抗流感病毒活性成分,其虚拟活性强于扎那米韦;3,3′,4-三甲氧基鞣花酸空间上与NA活性腔不匹配,虚拟活性最弱。本研究可为NA抑制剂的开发提供一定的理论指导。OBJECTIVE:To study the binding mode and interaction of 17 main antiviral components in Yinqiao powder with neuraminidase(NA).METHODS:The two-dimensional structure of 17 active components as glycyrrhizin,liquiritin,chlorogenic acid,3,3′,4-trimethoxy ellagic acid in Yinqiao powder and positive control zanamivir were transformed into three-dimensional structure by using CORINA,UCSF Chimera 1.3 and AutoDock Tools 1.5.4 molecular docking software.Then the grids of acceptor protein NA were set up,and the docking program was run to perform the docking operation.Using estimation inhibit constant(Ki)and binding energy(ΔGbind)as reference indexes,the difference of virtual activity of the docking moleculars were compared,and its reasons were analyzed from the docking conformation.RESULTS:In the 17 active components,Ki value for molecule docking of chlorogenic acid was 1.20μmol/L,andΔGbind was-8.08 kcal/mol(1 kcal=4.184 kJ),which was better than zanamivir(Ki 2.26μmol/L,ΔGbind-7.70 kcal/mol).Ki andΔGbind of 3,3′,4-trimethoxy ellagic acid were 149.41μmol/L and-5.22 kcal/mol,which were the worst among 17 compounds.Chlorogenic acid and zanamivir were more closely matched to the active sites of NA active cavity in space from the docking conformation,and occupied all the active chambers except S5,which presented a strong binding effect with NA.The docking conformation of 3,3′,4-trimethoxy ellagic acid was not strong as its plane structure restricted the combination with NA active sites.CONCLUSIONS:Chlorogenic acid is the strongest antiviral activity component in the Yinqiao powder,whose virtual activity is even stronger than zanamivir.The virtual activity of 3,3′,4-trimethoxy ellagic acid may be the weakest as its mismatching with the NA active cavity.This study may provide some theoretical guidance for the development of NA inhibitors.

关 键 词：银翘散 活性成分 抗病毒 神经氨酸酶 分子对接 

分 类 号：R287[医药卫生—中药学] R914.2[医药卫生—中医学]