基于网络药理学和分子对接法探寻黄连解毒汤治疗新型冠状病毒肺炎(COVID-19)活性化合物的研究

目的:基于网络药理学和分子对接技术,探寻黄连解毒汤治疗新型冠状病毒肺炎(COVID-19)的物质基础和作用机制。方法:利用TCMSP和Stitch及文献资料的检索,得到黄连解毒汤的化学成分和作用靶点。通过Cytoscape 3.3.0构建化合物-靶点网络图,Cludterirofiler对药物与疾病相同靶蛋白进行GO功能富集分析和KEGG通路富集分析。使用Autodock Vina软件进行分子对接,根据结合能和药物主要成分选择最佳的结合靶点。结果:研究共筛选出66个化合物和相应靶点239个,关键化合物主要有槲皮素、豆甾醇、山柰酚、汉黄芩素、谷甾醇、黄芩素、甲基黄连碱等,靶点涉及PTGS1、PTGS2、HSP90AA1、PRKACA、SCN5A等。GO功能富集分析生物过程主要集中于氧化应激、脂多糖、细菌的反应和凋亡信号通路的调节等。KEGG通路富集筛选信号通路(P<0.05),涉及糖尿病并发症中的AGE-RAGE信号通路、疱疹病毒感染、IL-17信号通路、TNF信号通路和甲型流感等。分子对接结果显示小檗碱、槲皮素、黄连碱、黄芩素主要化合物与SARS-CoV-2 3CL水解酶的结合能均高于参照药物的亲和力。结论:黄连解毒汤中的活性化合物能通过与新型冠状病毒3CL水解酶结合作用于PTGS2、HSP90AA1、ESR1等靶点调节,从而有可能对COVID-19有治疗作用。

Exploring the Active Compounds of Huanglian Jiedu Decoction in the Treatment of Coronavirus Disease 2019(COVID-19) Based on Network Pharmacology and Molecular Docking Method

Objective: To explore the material basis and mechanism of Huanglian Jiedu Decoction in the treatment of coronavirus disease 2019(COVID-19), by using network pharmacology and molecular docking technology. Methods: The chemical composition and action targets of Huanglian Jiedu Decoction studied by TCMSP, Stitch database and literature mining methods. Cytoscape 3.3.0 was used to construct the compound-target network map, The GO function enrichment and KEGG pathway analysis of the target protein was carried out by Cludterirofiler. Autodock Vina software was used for molecular docking, then the best binding target was selected according to the binding energy and the main components. Results: 66 compounds and 239 corresponding targets were screened, the key compounds were quercetin, stigmasterol, kaempferol, wogonin, beta-sitosterol, baicalein and worenine, etc, and the key targets involved PTGS1, PTGS2, HSP90 AA1, PRKACA and SCN5 A, etc. The function enrichment analysis of GO mainly focused on lipopolysaccharide, response to molecule of bacterial origin, response to oxidative stress and regulation of apoptotic signaling pathway. In KEGG pathway enrichment screening, AGE-RAGE signaling pathway in diabetic complications, Kaposi sarcoma?associated herpesvirus infection, IL-17 signaling pathway, TNF signaling pathway and Influenza A pathway were involved. Molecular docking results demonstrated that the binding energies of core compounds(berberine, quercetin, coptisine, baicalein) and COVID-19 coronavirus 3 CL hydrolase were higher than the affinity of the reference drug. Conclusion: The active compounds of Huanglian Jiedu Decoction can bind novel coronavirus 3 CL hydrolase on targets such as PTGS2, HSP90 AA1, and ESR1, which may have a therapeutic effect on COVID-19.