基于网络药理学与分子对接技术的金花清感颗粒防治新型冠状病毒肺炎的潜在药效物质研究

Exploring active compounds of Jinhua Qinggan Granules for prevention of COVID-19 based on network pharmacology and molecular docking

目的探究金花清感颗粒防治新型冠状病毒肺炎(COVID-19)的潜在物质基础。方法采用中药系统药理学分析平台(TCMSP)检索金花清感颗粒中11味药材所含化学成分与作用靶点。借助Uniprot数据库查询靶点对应基因,采用Cytoscape软件构建"药材-成分-靶点"网络,运用DAVID对相关靶点进行GO功能与KEGG通路富集分析。通过分子对接评价"药材-成分-靶点"网络中核心成分与新型冠状病毒(SARS-CoV-2)3CL水解酶及血管紧张素转化酶Ⅱ(ACE2)的结合作用。结果金花清感颗粒"药材-成分-靶点"网络包含154个化合物和276个相关靶点,关键靶点涉及PTGS2、HSP90AB1、HSP90AA1、PTGS1、NCOA2等。GO功能富集分析得到278个条目,主要涉及ATP结合、转录因子活化、细胞凋亡进程调控等。KEGG通路富集得到127条信号通路,涉及TNF、PI3K/Akt及HIF-1等与肺损伤保护相关通路。分子对接显示金花清感颗粒中芒柄花黄素、豆甾醇、β-谷甾醇、脱水淫羊藿素等核心成分与SARS-CoV-2 3CL水解酶及ACE2的亲和作用较好。结论金花清感颗粒可能通过多成分结合SARS-CoV-2 3CL水解酶及ACE2作用于PTGS2、HSP90AB1、HSP90AA1、PTGS1、NCOA2等靶点调节相关信号通路,从而防治COVID-19。

Objective To explore the effective chemical constituents of Jinhua Qinggan Granules for treatment of coronavirus disease 2019(COVID-19). Methods The compounds and action targets of eleven herbal medicines in Jinhua Qinggan Granules were collected via TCMSP. The genes corresponding to the targets were queried by the Uni Prot database, then the "herbal medicine-compound-target" network was established by Cytoscape software. The gene ontology(GO) function enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID to predict their mechanism. Molecular docking was used to analyze the binding force of the core effective compounds in the "herbal medicine-compound-target" network with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme Ⅱ(ACE2). Results The "herbal medicine-compound-target" network contained 154 compounds and 276 targets, and the key targets involved PTGS2, HSP90AB1, HSP90AA1, PTGS1, NCOA2, etc. GO function enrichment analysis revealed 278 items, including ATP binding, transcription factor activation and regulation of apoptosis process, etc. KEGG pathway enrichment screened 127 signaling pathways, including TNF, PI3K/Akt and HIF-1 signaling pathways related to lung injury protection. The results of molecular docking showed that formononetin, stigmasterol, beta-sitosterol, anhydroicaritin and other key compounds have a certain degree of affinity with SARS-CoV-2 3CL hydrolase and ACE2. Conclusion The effective compounds in Jinhua Qinggan Granules regulate multiple signaling pathways via binding ACE2 and acting on targets such as PTGS2, HSP90AB1, HSP90AA1, PTGS1, NCOA2 for the prevention of COVID-19.