基于网络药理学和分子对接探讨疏风解毒胶囊治疗新型冠状病毒肺炎可能的作用机制

Mechanism of Shufeng Jiedu Capsules in Treating Coronavirus Based on Network Pharmacology and Molecular Docking

目的采用网络药理学技术探讨疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的可能机制。方法利用中药系统药理学一体化分析平台(TCMSP)筛选疏风解毒胶囊活性成分和预测靶点,通过在线人类孟德尔遗传数据库(OMIM)、人类基因注释数据库(GeneCards)筛选COVID-19相关靶点,采用Cytoscape软件构建药物-靶点-疾病网络和靶点蛋白相互作用(PPI)网络,使用Autodock_vina软件进行分子对接验证,基于生物学信息注释数据库David数据库进行靶点基因本体(gene ontologg,GO)功能、京都基因和基因百科全书(KEGG)通路富集分析。结果筛选出疏风解毒胶囊活性成分190种,预测药物作用靶点299个,与COVID-19相关的靶点有52个。通过对药物-基因-疾病网络和PPI网络的拓扑学分析,筛选出白藜芦醇、葛根素、大黄素等8个核心活性成分和白细胞介素6(IL-6)、肿瘤坏死细胞因子(TNF)、丝裂原激活蛋白激酶8(MAPK8)和MAPK14个核心基因;富集到P≤0.05、伪发现率(FDR)≤0.05的GO条目130条,涉及脂多糖介导的信号通路、细胞因子活动、炎症反应、免疫反应等;富集到P≤0.05、FDR≤0.05的KEGG通路23条,涉及TNF信号通路、磷脂酰肌醇3-激酶/蛋白激酶B信号通路、NF-кB信号通路、低氧诱导因子-1信号通路、钙离子信号通路等。分子对接验证显示,核心活性成分与新型冠状病毒嵌合体和血管紧张素转换酶Ⅱ具有较好的结合活性。结论疏风解毒胶囊中的白藜芦醇、葛根素、大黄素等成分可能通过作用于血管紧张素转换酶Ⅱ、细胞丝氨酸蛋白酶影响病毒的入侵,从而对COVID-19具有一定的治疗作用。

Objective To explore the possible mechanism by which Shufeng Jiedu capsules can be used for treating the coronavirus(COVID-19)by using network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to screen the active ingredients and to predict targets of Shufeng Jiedu capsules.The COVID-19 related genes were screened via the Online Mendelian Inheritance in Man(OMIM)and The Human Gene Database(GeneCards),and the drug-targetdisease network and protein-protein interaction(PPI)network were constructed with Cytoscape software.Autodock_vina was used for molecular docking verification.GO(Gene Ontology)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment were analyzed based on David database.Results The results showed that 190 kinds of active ingredients in Shufeng Jiedu capsules were screened,and 299 predicted targets were selected.There were 52 targets that were intersected with COVID-19.Through the topological analysis of the drug-target-disease network and PPI network,eight core active components including resveratrol,puerarin,and quercetin were screened out,so were four core targets such as interleukin-6(IL-6),tumor necrosis factor(TNF),mitogen-activated protein kinase 8(MAPK8),and mitogen-activated protein kinase 1(MAPK1).A total of 130 GO entries with P≤0.05 and False Discovery Rate(FDR)≤0.05 were enriched,involving lipopolysaccharide-mediated signal pathways,cytokine activity,inflammatory response,and immune response.23 KEGG pathways with P≤0.05,FDR≤0.05,were enriched to TNF signal pathway,phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signal pathway,nuclear factor kappa-B(NF-кB)signaling pathway,hypoxia-inducible factor-1 quotation pathway,and calcium ion signaling pathway.Molecular docking verification showed that the core active components possessed good binding activity with the receptorbinding domain of virus chimera and angiotensin-converting enzyme.Conclusion Resveratrol,puerarin,emodin and other components of Shufeng Jiedu capsules may affect the invasion of virus by acting on ACE and cell serine protease,thus having therapeutic effect against COVID-19.