基于网络药理学和分子对接法探寻清宣止咳颗粒治疗儿童新型冠状病毒肺炎活性化合物

目的:探寻清宣止咳颗粒治疗儿童新型冠状病毒肺炎(COVID-19)的活性化合物。方法:借助中药系统药理学分析平台(TCMSP)检索清宣止咳颗粒中桑叶、薄荷、苦杏仁、桔梗、白芍、枳壳,陈皮、紫菀、甘草的化学成分和作用靶点。通过UniProt、GeneCards等数据库查询靶点对应的基因,进而运用Cytoscape 3.7.2构建化合物-靶点(基因)网络,通过DAVID进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制。结果:化合物-靶点网络包含141个化合物和相应靶点292个,关键靶点涉及PTGS2、ESR1、HSP90AA1、CALM1、AR等。GO功能富集分析得到GO条目339个(P<0.05),其中生物过程(BP)条目244个,细胞组成(CC)条目33个,分子功能(MF)条目62个。KEGG通路富集筛选得到96条信号通路(P<0.05),涉及小细胞肺癌、非小细胞肺癌、T细胞受体信号通路等。分子对接结果显示槲皮素、山柰酚、木犀草素等核心化合物与新冠病毒的亲和力与推荐用药相似。结论:清宣止咳颗粒中的有效活性成分可能通过作用于PTGS2、HSP90AA1、ESR1等靶点调节多条信号通路从而抑制新型冠状病毒肺炎作用。

Discussion on the Active Compounds of Qingxuan Zhike Granule in Treatment of Pediatric Coronavirus Disease 2019 Based on Network Pharmacology and Molecular Docking Method

To explore the active compounds of Qingxuan Zhike Granule for treatment of pediatric Coronavirus disease 2019 (COVID-19).Methods:With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),the chemical constituents and action targets of mulberry leaf,peppermint,bitter apricot seed,platycodon root,debark peony root,orange fruit,dried tangerine peel,tatarian aster root,liquorice root in Qingxuan Zhike granules were retrieved.The genes corresponding to the target were queried through databases such as UniProt and GeneCards,and then Cytoscape 3.7.2 was used to build a compound-target (gene) network,gene ontology (GO) function enrichment analysis was perform through DAVID,based on the Kyoto Encyclopedia of Genes and Genomes (KEGG ) Path enrichment analysis,its mechanism was predicted.Results:The compound-target network contains 141 compounds and 292 corresponding targets.The key targets are PTGS2,ESR1,HSP90AA1,CALM1,AR,etc.GO function enrichment analysis obtained 339 GO entries (P<0.05),of which 244 were biological process (BP) entries,33 were cell composition (CC) entries,and 62 were molecular function (MF) entries.The KEGG Path enrichment analysis obtained 96 signal pathways (P<0.05),involving small cell lung cancer,non-small cell lung cancer,and T cell receptor signaling pathways.The molecular docking results showed that the core compounds such as quercetin,Kaempferol,luteolin and the like had similar affinity to the COVID-19 virus as the recommended drugs.Conclusion:The active ingredients in Qingxuan Zhike granules may regulate multiple signaling pathways by acting on targets such as PTGS2,HSP90AA1,and ESR1,thereby inhibiting COVID-19.