基于网络药理学与分子对接探究荆芥-防风药对防治新型冠状病毒肺炎(COVID-19)的作用机制

Mechanism of Schizonepetae Herba-Saposhnikoviae Radix on the Prevention and Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking

目的:采用网络药理学与分子对接法探究荆芥-防风药对防治新型冠状病毒肺炎(COVID-19)的作用机制。方法:借助中药系统药理学分析平台TCMSP检索荆芥与防风的化学成分与作用靶标,采用Uniprot数据库查询各靶标对应的基因。通过String进行GO富集分析与KEGG通路富集分析,预测其作用机制。通过Omicshare绘制气泡图,运用Cytoscape软件构建化合物-靶标-通路网络并进行可视化分析。利用CB-Dock对核心活性化合物与COVID-19的3CL水解酶及ACE2进行分子对接。结果:以口服利用率OB≥30%,类药性DL≥0.18为活性化合物筛选条件,从荆芥-防风药中筛选出27个活性成分和212个靶标,与350个COVID-19相关靶标的交集靶标共有47个。其中,核心靶标25个,包含IL6、TP53、CASP3、MAPK1、CXCL8、CCL2等。核心化合物包括槲皮素、木犀草素、汉黄芩素、β-谷甾醇等。GO富集得出1381条结果,其中生物过程1210条,细胞组成54条,分子功能117条。KEGG通路富集得到相关通路160条,提示荆芥-防风药对可能作用于多条炎症、免疫、病毒感染相关通路,发挥防治COVID-19的作用。结论:通过网络药理学结合分子对接预测了荆芥-防风药对可通过槲皮素、木犀草素、汉黄芩素、β-谷甾醇等活性化合物,介导多条免疫、炎症、感染相关通路,进而发挥防治COVID-19的作用。

Objective:To explore the mechanism of Schizonepetae Herba-Saposhnikoviae Radixon the prevention and treatment of COVID-19 using network pharmacology and molecular docking.Methods:With the help of TCMSP,apharmacological analysis platform of Chinese medicine system,the chemical constituents and targets of Schizonepetae Herba and Saposhnikoviae Radix were retrieved,and the genes corresponding to each target were queried using Uniprot database.Perform GO enrichment analysis and KEGG pathway enrichment analysis through String to predict its mechanism of action.Use Omicshare to draw bubble charts,use Cytoscape software to build Compound-Target-Channel networks and analyze and visualize them.CB-Dock was used to molecularly dock the core active compounds with COVID-193 CL hydrolase and ACE2.Results:Use OB≥30%and DL≥0.18 as the screening conditions for active compounds,27 active ingredients and 212 targets were screened for Schizonepetae Herba-Saposhnikoviae Radix,there are 47 targets intersected with 350 COVID-19 related targets.Among them,25 core targets,including IL6,TP53,CASP3,MAPK1,CXCL8,CCL2 and so on.The core compounds are quercetin,luteolin,scutellarein,β-sitosterol and so on.GO enrichment yielded 1381 results,including 1210 biological processes,54 cells,and 117 molecular functions.The enrichment of the KEGG pathway resulted in 160 related pathways,suggesting that nepeta-parsnip may play a role in the prevention and treatment of COVID-19 against multiple pathways related to inflammation,immunity and viral infection.Conclusion:The network pharmacology combined with molecular docking predicts that Schizonepetae Herba-Saposhnikoviae Radixcan mediate multiple immune,inflammation,and infection-related pathways through active compounds such as quercetin,luteolin,begonin,andβ-sitosterol to play a role in the prevention and treatment of COVID-19.