基于网络药理学和分子对接研究疏风解毒胶囊治疗新型冠状病毒肺炎的机制

Mechanism of Shufeng Jiedu Capsule in the Treatment of Corona Virus Disease 2019 based on Network Pharmacology and Molecular Docking

目的:通过网络药理学和分子对接的方法探讨疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法:在TCMSP平台获取疏风解毒胶囊的活性成分和作用靶标;从2015年版中国药典获取药物的性味归经;从GeneCards数据库获取COVID-19的相关靶标基因并与疏风解毒胶囊的作用靶标取交集获取治疗靶标;将治疗靶标上传值STRING数据库获取蛋白互作网络;利用Cytoscape构建药材-性味归经网络、药材-活性成分-治疗靶标网络、蛋白质相互作用网络并分析;利用RStudio的clusterProfiler包进行GO、KEGG功能富集分析。结果:疏风解毒胶囊的8味中药主要归肺、肝、胃经,味苦性寒;得出179个活性成分共对应272个靶标,与COVID-19的共同靶标基因有53个,药材-活性成分-治疗靶标网络和蛋白质相互作用网络的共同关键基因为MAPK14和PTGS2;GO富集得出1 408条生物学过程、60条分子功能和22条细胞组分;KEGG功能富集得出155条通路,排名前20的通路中有11条与病毒、细菌和寄生虫的感染有关,如查加斯病、乙型肝炎、弓形虫病、利什曼病、甲型流感等;有3条与炎症免疫相关,分别为IL-17信号通路、TNF信号通路、Th17细胞分化;通过分子对接筛选出18个对2019-nCoV 3CL具有抑制作用活性成分和158个对ACE2具有抑制活性的化合物。结论:疏风解毒胶囊能通过多个组分、多靶点、多通路治疗新型冠状病毒肺炎,其机制可能与调控免疫炎症反应、抗病毒感染等相关,并且其活性成分具有潜在抗2019-nCoV和干扰2019-nCoV与ACE2结合的可能性。

Obiective: To explore mechanism of Shufeng jiedu capsule in the treatment of Corona Virus Disease 2019(COVID-19) based on network pharmacology and molecular docking.Methods: The active components and targets of Shufeng jiedu capsule were obtained from TCMSP platform.The drug′s nature flavor and channel tropism were obtained from the 2015 edition of "Chinese Pharmacopoeia".The relevant target genes of COVID-19 were obtained from GeneCards database and the therapeutic target was obtained from the intersection of the target and the action target of Shufeng jiedu capsule.The protein interaction network was obtained by uploading the therapeutic target value to STRING database.Cytoscape was used to construct and analyze the network of medicinal materials-nature flavor and channel tropism, the network of medicinal materials-active components-therapeutic targets and the network of protein interaction.ClusterProfiler package in RStudio was used for GO and KEGG function enrichment analysis.Results: The eight traditional Chinese medicine in Shufeng jiedu capsule mainly attributed to the lung, liver and stomach meridians, bitter, cold.179 active components corresponded to 272 targets, and there were 53 common target genes with COVID-19.MAPK14 and PTGS2 were the common key genes in the network of medicinal materials-active components-therapeutic targets and the network of protein interaction.GO enrichment resulted in 1 408 biological processes, 60 molecular functions and 22 cell components.155 pathways were obtained by KEGG functional enrichment, 11 of the top 20 pathways were related to viral, bacterial and parasitic infections, such as Chagas disease, Hepatitis B,Toxoplasmosis, Leishmaniasis and influenza A,etc.Three of them were related to inflammatory immunity, namely IL-17 signaling pathway, TNF signaling pathway and Th17 cell differentiation.Eighteen compounds with inhibitory activity against 2019-nCoV and 158 compounds with inhibitory activity against ACE2 were screened by molecular docking.Conclusion: Shufeng jiedu capsule can treat COVID-19 through multiple components, multiple targets and multiple pathways, and its mechanism may be related to the regulation of immune inflammatory response, antiviral infection, etc.its active ingredients have the potential to resist 2019-nCoV and interfere with the possibility of binding of 2019-nCoV to ACE2.