基于网络药理学与化学成分研究的连花清瘟胶囊治疗新型冠状病毒肺炎（COVID-19）作用机制探讨＊

目的 通过网络药理学与分子对接的方法,根据最新研究进展,探讨连花清瘟胶囊治疗新型冠状病毒肺炎（COVID-19）的作用机制。方法 纳入相关化学成分研究,从中明确连花清瘟胶囊内所含有的化学成分与入血成分信息;于TCMSP、STITCH数据库搜索药物作用靶点蛋白后使用UniProt数据库进行相关转化;通过GeneCards、DisGeNET、UniProt数据库筛选COVID-19相关靶点,同时利用PubMed数据库搜索SARS-CoV-2病毒全基因组信息;将药物有效成分作用靶点与疾病靶点比对筛选后构建连花清瘟内有效化合物治疗COVID-19的核心成分-靶点相互作用网络图;利用STRING平台对核心靶点进行PPI网络分析,找出关键靶点信息;使用CytoScape插件ClueGo对核心靶点进行GO功能富集分析与KEGG通路富集分析;将核心成分与相关受体通过Autodock Vina软件进行分子对接分析。结果 筛选出连花清瘟胶囊中25个活性成分和146个潜在靶点,新冠肺炎相关靶点为122个,经比对后选出与连花清瘟胶囊治疗新冠肺炎核心作用靶点为26个;通过PPI网络数据选出IL6、IL10、TNF、CCL2、DPP4等核心靶点,KEGG通路与GO富集分析筛选出17条信号通路,7个相关的生物进程;分子对接结果显示大黄素、芦荟大黄素、山奈酚、芦丁等成分同与ACE2结合的SARS-CoV-2刺突蛋白受体结合域结合能较强。结论 通过网络药理学证实了连花清瘟胶囊多成分、多靶点、整体调节的作用特点,预测了LQC治疗COVID-19的主要可能的作用机制,为其活性成分研究和实验研究提供理论依据,并有助于阐明连花清瘟胶囊对新冠肺炎的治疗原理。

The Mechanism of Lianhua Qingwen Capsule for the Treatment of Coronavirus disease 2019 (COVID-19) Based on Network Pharmacology and Chemical Composition Research

Objective To explore the mechanism of Lianhua Qingwen Capsule (LQC) for treating coronavirus disease-19 by network pharmacology and molecular docking methods as well as according to the latest research progress.Methods Incorporate relevant chemical composition research to clarify the chemical composition and blood composition information contained in Lianhua Qingwen Capsule; Search the drug target protein in TCMSP and STITCH database and use UniProt database to carry out relevant transformation; Screening for COVID-19 related targets through GeneCards, DisGeNET, UniProt databases, and using the PubMed database to search SARS-CoV-2 virus genome information; After screening the target of the active ingredient of the drug and the target of the disease, construct the core component-target interaction network diagram of the effective compound in the Lianhua Qingwen capsule to treat COVID-19; Use STRING database to perform PPI network analysis on core targets to find out key target information; Use CytoScape plugin ClueGo to perform GO function enrichment analysis and KEGG pathway enrichment analysis on core targets; The core components and related receptors were analyzed by Autodock Vina software for molecular docking.Results 25 active ingredients and 146 potential targets in Lianhua Qingwen Capsule were screened out. COVID-19 related targets were 122. After comparison, the core action targets of LQC in treating COVID-19 were 26; The core targets such as IL6, IL10, TNF, CCL2 and DPP4 were selected through PPI network data. The KEGG pathway and GO enrichment analysis screened out 17 signal pathways and 7 related biological processes; Molecular docking results show that emodin, aloe-emodin, kaempferol, rutin have binding energy to SARS-CoV-2 spike receptorbinding domain bound to the ACE2 receptor.Conclusion Through the network pharmacology, the multi-component, multi-target, and overall regulation of Lianhua Qingwen Capsule have been confirmed, and the main possible mechanism of LQC treatment for COVID-19 has been predicted, providing a theoretical basis for its active ingredient research and experimental research. It also helps to elucidate the treatment principle of Lianhua Qingwen Capsule on COVID-19.