基于网络药理学及分子对接技术研究疏风解毒胶囊治疗新型冠状病毒肺炎的潜在靶标及机制

The Potential Targets and Mechanisms of Shufeng Jiedu Capsule(疏风解毒胶囊)for Novel Coronavirus Pneumonia(COVID-19)based on Network Pharmacology and Molecular Docking

目的:运用网络药理学及分子对接技术探究疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的潜在分子机制。方法:检索计算系统生物学实验室数据库和分析平台(TCMSP)获得疏风解毒胶囊所有有效活性成分的干预靶点,并与GeneCards数据库中的新型冠状病毒肺炎疾病基因靶标相映射得到交集靶标;通过Cytoscape3.7.0构建“药物-活性成分-靶标”网络;通过String得到交集靶标的PPI网络;运用数据包进行基因本体(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。将疏风解毒胶囊中关键有效成分化合物与PPI中核心蛋白进行分子对接。结果:“药物-活性成分-靶标”网络图中涉及交集靶标48个,关键性化合物主要包括槲皮素、木犀草素、山柰酚、汉黄芩素、刺槐黄素,关键靶点涉及CALM1、NOS2、PTGS2、DPP4、PTGS1等。GO富集分析包括1335条生物过程(biological process,BP)、34条细胞组分(cellular component,CC)以及86项分子功能(molecular unction,MF)。18条KEGG相关通路,涉及病毒蛋白与细胞因子和细胞因子受体的相互作用等。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核心靶蛋白亲和力较高。结论:疏风解毒胶囊中的化学成分通过与关键靶蛋白IL-6、ALB、MAPK3等结合涉及多种生物学过程及通路治疗COVID-19。

Objective:To investigate the potential target and mechanism of Shufeng Jiedu Capsule for Novel coronavirus pneumonia(COVID-19)by using network pharmacology and molecular docking technique.Methods:The active components of Shufeng Jiedu Capsule were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,and the target genes of active components were selected by AMDE parameters.The relevant target genes of Novel coronavirus pneumonia were retrieved from OMIM and Gene Cards database,and the target genes of active components were matched with Shufeng Jiedu Capsule to obtain the target genes of intersection target.The"drug-component-disease-target"network map was constructed by using Cytoscape 3.7.0,and the PPI network of intersection target was obtained bySTRING.R language and related packets were used for GO,KEGG analysis.Using PubChem,the PDB database,and AutoDuck software,PPI's top-ranked proteins were linked molecularly to the highest confidence compounds.Results:A network diagram of"drug-active components-targets"involves 48 intersecting targets.Key compounds include quercetin,luteolin,kaempferol,baicalein,Robinia pseudoacacia flavin and key targets involving CALM1,NOS2,PTGS2,DPP4,and PTGS1.GO enrichment analysis included 1335 biological processes(biological process,BP),34 cellular components(cellular component,CC),and 86 molecular functions(molecular unction,MF).Acquired obtained 18 KEGG related pathways involving the interaction of viral proteins with cytokines and cytokine receptors.Molecular docking results showed that quercetin,kaempferol,luteolin and other core compounds had high affinity with core target proteins.Conclusion:The chemical components in Shufeng Jiedu capsule involve a variety of biological processes and pathways to treat COVID-19 by combining with key target proteins IL-6,ALB,MAPK3,etc.