基于网络药理学及分子对接技术分析“防疫清肺汤”用于防治新冠肺炎(COVID-19)相关肺肾损伤的物质基础

Study on Mechanism of Fangyi Qingfei Decoction Against COVID-19 Associated Lung-kidney Injury Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学和分子对接的方法,初步探讨防疫清肺汤在新型冠状病毒肺炎(COVID-19)治疗中缓解肺肾损伤及抗病毒的物质基础。方法:从TCMSP数据库收集防疫清肺汤的成分和作用靶点;Genecards数据库收集肺肾损伤相关靶点,并与药物靶点取交集;String数据库构建蛋白相互作用网络并分析潜在核心靶点,DAVID数据库进行GO富集分析和KEGG通路富集分析;Cytoscape软件构建成分-靶点-通路网络图;分子对接技术评估活性成分与核心靶点、SARS-COV-23CL水解蛋白酶(Mpro)以及血管紧张素转化酶2(ACE2)结合情况。结果:网络药理学分析表明,防疫清肺汤共筛选出159种活性成分,肺肾损伤相关靶点227个;GO富集到生物过程条目123个(P<0.05),KEGG富集到通路条目75个(P<0.05)。分子对接结果表明,防疫清肺汤的核心活性成分山柰酚、槲皮素、汉黄芩素、木犀草素、刺槐素与核心靶点AKT1、ALB、IL6、TP53、VEGFA、TNF、JUN、CASP3、EGFR、MAPK1及Mpro、ACE2均有较强结合能力。结论:防疫清肺汤可以通过多成分、多通路及多靶点缓解COVID-19引起的肺肾损伤,并通过结合Mpro、ACE2发挥抗病毒作用。

Objective:To explore the potential antivirus and reducing lung-kidney injury mechanisms of Fangyi Qingfei Decoction(FYQFD)on coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking method.Methods:TCMSP databases were used to search the compounds and targets of FYQFD,and Genecards database was used to search the targets of acute lung-kidney injury.The intersection method was used to obtain the targets related to the therapeutic effect of FYQFD.Protein-protein interaction(PPI)network was constructed by STRING database and the hub target genes were identified by calculating node degree.Molecular docking was performed based on the hub compounds and hub target gens and the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)3CL hydrolase(Mpro)and angiotensin converting enzyme II(ACE2).Results:Total 159 potential active components were screened from FYQFD,corresponding to 203 targets associated lung and kidney injury.GO function enrichment analysis revealed 123 biological process(BP)items(P<0.05),75 signal pathways(P<0.05)were screened out after KEGG pathway enrichment analysis.Furthermore,molecular docking indicated that main active compounds kaempferol,quercetin,wogonin,luteolin and acacetin in FYQFD exhibited higher affinity with AKT1,ALB,IL6,TP53,VEGFA,TNF,JUN,CASP3,EGFR,MAPK1,SARS-CoV-23CL hydrolase(Mpro),ACE2.Conclusion:The compounds in FYQFD can bind with Mpro and ACE2,and acting on many targets to regulate multiple signaling pathways,thus exerting the therapeutic effect on COVID-19.