基于网络药理学和分子对接法探寻达原饮治疗新型冠状病毒肺炎(COVID-19)活性化合物的研究

Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method

目的探寻达原饮治疗新型冠状病毒肺炎(COVID-19)的活性化合物。方法借助中药系统药理学分析平台(TCMSP)检索达原饮中槟榔、厚朴、草果、知母、白芍、黄芩、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Cytoscape3.2.1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267个,关键靶点涉及PTGS2、HSP90AA1、ESR1、AR、NOS2等。GO功能富集分析得到GO条目522个(P<0.05),其中生物过程(BP)条目421个,细胞组成(CC)条目38个,分子功能(MF)条目63个。KEGG通路富集筛选得到25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、黄芩素等核心化合物与COVID-19推荐用药的亲和力相似。结论达原饮中的活性化合物可能通过与血管紧张素转换酶II(ACE2)结合作用于PTGS2、HSP90AA1、ESR1等靶点调节多条信号通路,从而有可能对COVID-19有治疗作用。

Objective To explore the active compound of Da-Yuan-Yin for treatment of coronavirus disease 2019(COVID-19). Methods Based on traditional Chinese medicine system pharmacology platform(TCMSP), the chemical composition and targets of Arecae Semen, Magnoliae Officinalis Cortex, Tsaoko Fructus, Anemarrhenae Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, and Glycyrrhizae Radix et Rhizoma were screened. The targets of corresponding gene were searched through UniProt, GeneCards databases, and then Cytoscape3.2.1 was used to build compound-targets(genes) networks. The enrichment of gene ontology(GO) function analysis by DAVID and the pathway enrichment analysis by Kyoto Encyclopedia of Genes and Genomes(KEGG) were carried out, the mechanism of its action was predicted. Results The compound-target network contained 141 compounds and 267 corresponding targets, and the key targets involved PTGS2, HSP90 AA1, ESR1, AR, NOS2, etc. The function enrichment analysis of GO was 522(P < 0.05), of which there were 421 biological processes(BP) items, and 38 related items of cell composition(CC),and 63 molecular function(MF) items. There were 25 signal pathways(P < 0.05) in the KEGG pathway enrichment screening, involving small cell lung cancer, non-small cell lung cancer and T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, baicalin and other core compounds was similar to recommended drugs recommended in the treatment of COVID-19. Conclusion The active compounds in Da-Yuan-Yin may regulate multiple signaling pathways by binding angiotensin converting enzyme II(ACE2) and acting on targets such as PTGS2, HSP90 AA1 and ESR1 to inhibit COVID-19.