基于网络药理学及分子对接探讨半夏-藿香抗新型冠状病毒肺炎作用机制

Mechanism of Pinelliae Rhizoma-pogostemonis Herba Against COVID-19 Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学筛选半夏-藿香药对治疗新型冠状病毒肺炎(COVID-19)的潜在活性成分、核心靶点、信号通路。方法:通过中药系统药理学数据库与分析平台(TCMSP)筛选半夏-藿香药对活性成分和靶点,与GeneCards、NCBI数据库中COVID-19基因集相互映射获取关键靶点,同时通过STRING数据库和Cytoscape 3.6.1软件构建关键靶点相互作用网络。利用DAVID数据库进行基因本体(GO)-生物过程(BP)及KEGG通路富集分析,获得分子对接证据支持。结果:半夏-藿香药对有效活性成分24个,关键靶点45个,共富集出生物过程、细胞组分和分子功能条目443条,通路103条。分子对接结果显示在半夏-藿香药对中,与3CLpro结合最好的是β-谷甾醇;与血管紧张素转换酶2结合最好的为槲皮素。结论:半夏-藿香药对关键化合物可能从结构上作用于严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)入侵及从多成分多靶点多通路抑制细胞因子风暴,广谱抗病毒、抑菌及免疫调节,干预网状激活系统起到治疗作用。

Objective:To screen the potential active components,core targets,and signaling pathways of Pinelliae Rhizoma-Pogostemonis Herba for the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology.Methods:The active components and targets of Pinelliae Rhizoma-Pogostemonis Herba were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the key targets were obtained by mutual mapping with COVID-19 gene sets in GeneCards and NCBI.Meanwhile,the key target interaction network was constructed by STRING and Cytoscape 3.6.1.Enrichment analysis of Gene Ontology(GO)-biological process(BP)and KEGG pathways was performed using DAVID,which was supported by molecular docking evidence.Results:There were 24 active components and 45 key targets of Pinelliae Rhizoma-Pogostemonis Herba,443 entries of biological processes,cellular components,and molecular functions,and 103 pathways.Molecular docking results showed that in Pinelliae Rhizoma-Pogostemonis Herba,β-sitosterol and quercetin showed best binding to 3CLpro and angiotensin-converting enzyme 2(ACE2),respectively.Conclusion:The key compounds of Pinelliae Rhizoma-Pogostemonis Herba may structurally act on the invasion of the severe acute respiratory syndrome(SARS)-CoV-2 and inhibit cytokine storm from multiple components,multiple targets,and multiple pathways.Pinelliae Rhizoma-Pogostemonis Herba exert the therapeutic role by virtue of broad-spectrum antiviral,antibacterial,immunomodulatory effects and intervening in the reticular activation system.