基于计算机辅助药物设计探究扶正避瘟方预防新型冠状病毒感染的物质基础及分子机制

Exploration of Material Basis and Molecular Mechanism for Preventing SARS-CoV-2 Infection by Fuzheng Biwen Prescription Based on Computer Aided Drug Design

目的从抑制病毒感染不同靶点的选择性、调控机体免疫因子的角度出发,系统研究扶正避瘟方预防新型冠状病毒(SARS-CoV-2)感染的物质基础及分子机制。方法采用计算机辅助药物设计中的同源模建、分子对接等方法,对扶正避瘟方中各药味的化合物进行基于分子对接的虚拟筛选。运用靶点反向预测及其KEGG通路,分析方中健脾药白术对机体抵御病毒的潜在靶点和分子机制,并进行分子对接验证。结果扶正避瘟方中阻断SARS-CoV-2入侵的活性成分有84个,连翘、生姜、荷叶、黄芪对SARS-CoV-2感染具有针对性阻断作用。对不同冠状病毒阻断机制的差异性分析显示,荷叶对SARS-CoV的选择性高于SARS-CoV-2,生姜则对SARS-CoV-2更具针对性。白术缺乏直接阻断成分,但白术内酯Ⅲ、苍术酮和茅苍术醇等与免疫靶点大麻素受体2(CB2)有较强的潜在结合能力。结论扶正避瘟方中连翘、荷叶的单体成分连翘脂苷A、(-)-儿茶素、熊竹素等可作为潜在抗病毒成分进一步开发,白术中的白术内酯Ⅲ等可能通过结合免疫靶点CB2发挥免疫调控作用。

Objective To systematically study the material basis and molecular mechanism of the prevention of SARS-CoV-2 infection by Fuzheng Biwen Prescription from the perspective of inhibiting the selection of virus infection and regulating the body’s immune factors.Methods Homologous modeling and molecular docking were used to screen the compounds of various kinds of Chinese materia medica in Fuzheng Biwen Prescription based on molecular docking.Meanwhile,the reverse target prediction and KEGG pathway were used to analyze the potential targets and molecular mechanism of Astractylodis Macrocephalae Rhizoma in the body to resist virus,and the molecular docking was verified.Results There are 84 active ingredients which could block the invasion of SARS-CoV-2.Forsythiae Fructus,Zingiberis Rhizoma Recens,Nelumbinis Folium,and Astragali Radix had targeted blocking effects on SARS-CoV-2.Differential analysis of different coronavirus blocking mechanisms showed that Nelumbinis Folium was more selective for SARS-CoV than SARS-CoV-2,and Zingiberis Rhizoma Recens was more targeted for SARS-CoV-2.Astractylodis Macrocephalae Rhizoma lacked direct blocking components,but atractylodesⅢ,atractylone and atractylol had strong potential binding ability to immune targets cannabinoid receptor 2(CB2).Conclusion The monomer components such as Forsythoside A,(-)-Catechin and 5,4'-dihydroxy-3,7-dimethoxyflavone in Forsythiae Fructus and Nelumbinis Folium in Fuzheng Biwen Prescription can be further developed as a potential anti-viral ingredient;atractylodesⅢmay play a role in immune regulation by binding the immune target CB2.