基于分子对接和网络药理学探讨金银花防治新型冠状病毒肺炎潜在作用机制

Study on the potential mechanism of Lonicerae japonicae Flos against COVID-19 based on molecular docking and network pharmacology

中文关键词:  金银花  新型冠状病毒肺炎  分子对接  网络药理学

英文关键词:Lonicerae japonicae Flos  COVID-19  molecular docking  network pharmacology

中文摘要:

      目的 基于分子对接和网络药理学探讨金银花防治新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的潜在作用机制。方法 利用AutoDock Vina将金银花中14种化学成分与新型冠状病毒(Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2)S蛋白受体结合结构域与血管紧张素转化酶 II(angiotensin I converting enzyme 2, ACE2)蛋白酶结构域复合物(Severe Acute Respiratory Syndrome Coronavirus 2 spike receptor-binding domain bound to the angiotensin I converting enzyme 2 receptor, SARS-CoV-2-S-RBD-ACE2)进行分子对接。利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)获取上述14种化学成分的作用靶点, 使用GeneCards及美国国家生物技术信息中心(National Center for Biotechnology Information, NCBI)数据库获取COVID-19靶点, 将药物与疾病交集靶点导入Cytoscape 3.7.0软件建立药物-化学成分-靶点-疾病网络, 导入STRING数据库获取靶点蛋白质相互作用(protein protein interaction, PPI)网络, 导入Bioconductor进行基因本体(gene ontology, GO)功能注释和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析。结果 分子对接结果显示金银花中14种化学成分与SARS-CoV-2-S-RBD-ACE2均有较好的结合活性, 其中12种成分结合活性优于诊疗方案中4种COVID-19治疗药物; 网络药理学结果显示金银花8种成分可通过干预46个靶点、149条通路发挥防治COVID-19的作用。结论 金银花中多种化学成分可能通过与SARS-CoV-2-S-RBD-ACE2结合, 影响复合物的稳定性, 从而发挥治疗COVID-19的作用。金银花治疗COVID-19具有多成分、多靶点、多途径的特点, 对COVID-19引起的免疫系统紊乱、炎症等具有潜在的治疗作用, 研究结果可为金银花防治COVID-19作用机制提供一定的理论基础与科学依据。

英文摘要:

      Objective To discuss the potential mechanism of Lonicerae japonicae Flos on COVID-19 (Corona Virus Disease 2019) based on molecular docking and network pharmacology. Methods The 14 compounds in L. japonicae Flos were used for molecular docking with the SARS-CoV-2-S-RBD-ACE2 (severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain bound to the angiotensin I converting enzyme 2 receptor) by AutoDock Vina. TCMSP (traditional chinese medicine systems pharmacology database and analysis platform) was used to obtain the target of the 14 components above. GeneCards and NCBI (National Center for Biotechnology Information) were used to obtain the target of COVID-19. The intersection target of drug and disease was introduced into Cytoscape 3.7.0 software to create a drug-compound component-target-disease network, was introduced into STRING and Cytoscape 3.7.0 software to establish and analyze the PPI (protein protein interaction) network, and was introduced into Bioconductor to analyze the GO (gene ontology) function and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment of the targets. Results The results of molecular docking showed that 14 components of L. japonicae Flos had good binding activity with SARS-CoV-2-S-RBD-ACE2, and the binding activity of 12 components were better than that of 4 COVID-19 drugs in the treatment plan. The results of network pharmacology showed that 8 components of L. japonicae Flos could prevent and control COVID-19 by intervening 46 targets and 149 pathways. Conclusion Many components in L. japonicae Flos could have COVID-19 therapeutic effect by affecting the stability of SARS-CoV-2-S-RBD-ACE2. The treatment of COVID-19 with L. japonicae Flos has the characteristics of multi-component, multi-target and multi-channel, which has potential prevention and treatment effect on immune system disorder and inflammation caused by COVID-19. The research results can provide certain theoretical basis and scientific basis for the prevention and treatment of COVID-19 by Chinese medicine.