网络药理学及分子对接方法预测避瘟丹防治新冠病毒肺炎的作用机制

Mechanism of action of the active constituents of Biwen Dan on novel coronavirus disease:A study based on network pharmacology and molecular docking

目的:基于网络药理学和分子对接技术分析避瘟丹抗新冠病毒肺炎的作用机制。方法:利用中药系统药理学分析平台(TCMSP)筛选避瘟丹中药物的活性成分。从TCMSP数据库获得成分及靶点信息。在Gene Cards与OMIM数据库,以“Novel coronavirus pneumonia”为关键词检索,收集与COVID-19相关的作用靶点。运用Cytoscape3.8.2构建药物-活性成分-靶点网络,筛选避瘟丹中的关键成分。通过STRING数据库构建靶点蛋白相互作用(PPI)网络,筛选避瘟丹治疗新型冠状病毒肺炎的核心靶点;通过DAVID网站对得到的潜在作用靶点进行GO和KEGG富集分析;分子对接验证核心活性成分与关键靶点对接活性。结果:通过TCMSP数据库检索后,获得活性成分有117个,所涉及靶点有238个;通过Gene Cards和OMIM数据库检索后,共获得1008个疾病靶点;取活性成分靶点与疾病靶点交集78个,作为避瘟丹防治COVID-19作用靶点;制作药物-有效成分-靶点药理网络图,包含了104个化合物节点和238个潜在靶点节点,排名最靠前的5个化合物分别是槲皮素、山柰酚、汉黄芩素、7-甲氧基-2-甲基异黄酮和异鼠李素;蛋白互作网络共78个点,1318条连线,其中度(degree)值排名前5个靶点分别为TNF、AKT1、TP53、IL6、IL1B;所富集出的条目共计585个,其中生物过程条目466个,细胞组成条目40个,分子功能条目79个;KEGG通路分析获得122条通路,其中值得关注的通路有TNF signaling pathway、Coronavirus disease-COVID-19;分析对接表明结合能最低的前六个对接结果分别是7-甲氧基-2-甲基异黄酮和AKT1、槲皮素和ACE2、山柰酚和ACE2、汉黄芩素和AKT1、异鼠李素和ACE2、异鼠李素和AKT1。结论:网络药理学预测及分子对接验证的结果提示,避瘟丹可能通过Coronavirus disease-COVID-19、IL-17、TNF-α、Toll-like receptor通路发挥防治新冠病毒肺炎的作用。

Objective:This study used network pharmacology and molecular docking to investigate the mechanism of action of Biwen Dan against novel coronavirus disease(COVID-19)by screening for core active ingredients and targets of Biwen Dan and predicting their biological processes and signaling pathways involved in COVID-19.Methods:The TCM Systematic Pharmacology Analysis Platform(TCMSP)was utilized to screen the active ingredients of the drugs in Biwen Dan.Composition and target information were obtained from TCMSP database.The GeneCards and OMIM databases were searched with the keyword"Novel coronavirus pneumonia"to collect the targets related to COVID-19.Cytoscape 3.8.2 was used to construct a drug-active ingredient-target network to screen the key components of the drug.The target protein interaction(PPI)network was constructed through the STRING database to screen the core targets of Biwen Dan for the treatment of novel coronavirus pneumonia.The potential targets obtained were analyzed by GO and KEGG enrichment through the DAVID website,and molecular docking was performed to verify the docking activities of the core active ingredients and the key targets.Results:After searching the TCMSP database,117 active ingredients and 238 targets were obtained.After searching the GeneCards and OMIM databases,a total of 1,008 disease targets were obtained.78 intersections of active ingredient targets and disease targets were taken as the targets of Biwen Dan for COVID-19 prevention and treatment,and a drug-active ingredient-target pharmacology network diagram was produced,containing 104 compound nodes and 238 potential target nodes,the top five compounds were quercetin,kaempferol,baicalein,7-methoxy-robin and other compounds.The network diagram contained 104 compound nodes and 238 potential target nodes,and the top 5 compounds were quercetin,kaempferol,baicalein,7-methoxy-2-methylisoflavone,and isorhamnetin.The protein interactions network consisted of 78 points and 1,318 connecting lines,of which the top 5 targets in terms of degree value were TNF,AKT1,TP53,IL6,ILIB,IL6,and IL1B,and the top 5 targets were TNF,AKT1,and TP53,respectively,IL6,IL1B.The total number of enriched entries was 585,including 466 entries for biological processes,40 entries for cellular components,and 79 entries for molecular functions.KEGG pathway analysis yielded 122 pathways,of which those of interest were TNF signaling pathway,Coronavirus disease-COVID-19.The top six docking results analyzing the docking showed the lowest binding energy were 7-methoxy-2-methylisoflavone and AKT1,quercetin and ACE2,kaempferol and ACE2,Wogonin and AKT1,isorhamnetin and ACE2,and isorhamnetin and AKT1,respectively.Conclusion:Pharmacological network predictions and molecular docking suggest that Biwen Danon has potential therapeutic effects on COVID-19 through the coronavirus disease-COVID-19,IL-17,TNF-α,Toll-like receptor pathways.