基于网络药理学和分子对接技术的玉屏风散防治新型冠状病毒肺炎活性化合物研究

目的:基于网络药理学和分子对接技术探讨玉屏风散防治新型冠状病毒肺炎的活性化合物。方法:通过TCMSP数据库检索玉屏风散中黄芪、防风、白术的活性化合物,并筛选出药物成分作用靶点;通过Uniprot、GeneCards等数据库查询靶点对应的基因。通过Cytoscape 3.7.2软件和STRING数据库构建药物-化合物-靶点网络、靶标蛋白互作PPI网络。利用DAVID数据库对核心靶点进行GO富集和KEGG通路注释分析,预测其作用机制。最后将重要活性化合物与SARS-CoV-2 3CL水解酶及ACE2进行分子对接。结果:药物-化合物-靶点网络中包含药物3个、化合物30个和相应靶点115个。GO功能富集分析得到GO条目1 595个(P<0.05),其中生物过程(BP)条目1 372个,细胞组成(CC)条目78个,分子功能(MF)条目145个。KEGG通路富集筛选得到121条信号通路(P<0.05),涉及前列腺癌、乳腺癌、胃癌、非小细胞肺癌、小细胞肺癌等。分子对接结果显示玉屏风散中山柰酚、黄花菜木脂素A、常春配基等核心活性化合物与SARS-CoV-2 3CL水解酶和ACE2具有一定的亲和力。结论:玉屏风散中的核心活性化合物能通过与ACE2结合作用于ESR1、AR、PTGS2等靶点调节多条信号通路,从而发挥对COVID-19的防治作用。

Study on Active Compounds of Yupingfeng San for Preventing and Treating COVID-19 Based on Network Pharmacology and Molecular Docking Technology

Objective: To explore the active compounds of Yupingfeng San in preventing and treating COVID-19 based on network pharmacology and molecular docking technology. Methods: The active compounds of Astragalus membranaceus, Saposhnikovia divaricata and Atractylodes macrocephala Koidz in Yupingfeng San were searched through TCMSP database, and the action targets of drug compounds were screened. Genes corresponding to the targets were queried through Uniprot, GeneCards and other databases. The drug-compound-target network and target protein interaction PPI network were constructed through the Cytoscape 3.7.2 software and STRING database. DAVID database was used for GO enrichment and KEGG pathway annotation analysis of core targets to predict their mechanism of action. Finally, the important active compounds were molecular docked with SARS-CoV-2 3 CL hydrolase and ACE2. Results: 3 drugs, 30 compounds and 115 corresponding targets were included in the drug-compound-target network. The enrichment analysis of GO functions yielded 1595 GO entries(P<0.05), including 1372 biological process(BP), 78 cell composition(CC) and 145 molecular function(MF). The KEGG pathway was enriched and screened to obtain 121 signal pathways(P<0.05), which involved in prostate cancer, breast cancer, gastric cancer, non-small cell lung cancer, small cell lung cancer, etc. Molecular docking results showed that the core active compounds such as kaempferol, cleomiscosin A and hederagenin in Yupingfeng San had certain affinity with SARS-CoV-2 3 CL hydrolase and ACE2. Conclusion: The core active compounds in Yupingfeng San can regulate multiple signal pathways by binding with ACE2 to ESR1, AR, PTGS2 and other targets, to play a prevent and treatment for COVID-19.