基于网络药理学和分子对接的陈皮干预COVID-19的可能机制

Possible Mechanism of Citri Reticulatae Pericarpium intervening on COVID-19 Based on Network Pharmacology and Molecular Docking

目的:运用网络药理学及分子对接技术,筛选陈皮中与人类新型冠状病毒3CL水解酶及ACE2受体蛋白结合能力较好的活性成分,研究其干预COVID-19的潜在分子机制,为中药单体成分治疗新冠肺炎药物的研发提供参考。方法:利用TCMSP数据库获取陈皮活性成分及靶标,利用GeneCards数据库获取新冠肺炎相关靶标,通过韦恩图获取陈皮与新冠肺炎交集靶点,在STRING数据库进行交集靶点的蛋白网络互作,运用数据包进行GO富集和KEGG通路富集分析,最后通过分子对接技术,将陈皮核心化学成分与SARS-CoV-23CL水解酶及ACE2受体对接,筛选出结合能力较好的化学成分。结果:获得陈皮有效化学成分5个,陈皮与新冠肺炎的交集靶点15个,PPI网络主要涉及MAPK、MAPK8、CASP3、MAPK1、PTGS2、CAT、PPARG、NOS2等核心靶蛋白;GO功能富集分析,得到生物过程条目898个,细胞组成条目35个,分子功能条目70个(P<0.05);KEGG富集得139条通路(P<0.05),主要涉及肺结核、乙型肝炎、卡波济氏肉瘤疱疹病毒感染等通路;分子对接筛选得到与SARS-CoV-23CL水解酶及ACE2受体结合能力较好的活性成分是柚皮素和陈皮素。结论:陈皮中筛选出的关键活性成分(柚皮素和陈皮素)与SARS-CoV-23CL水解酶蛋白(Mpro)和ACE2受体有结合潜力,陈皮或可通过抗病毒、抗炎、调控细胞凋亡、调节免疫等途径,发挥抑制肺纤维化的作用。

Objective:To screen active components with better binding activity to human novel coronavirus 3CL hydrolase and ACE2 receptor protein in Citri Reticulatae Pericarpium,and study the potential molecular mechanism of intervention on COVID-19 based on network pharmacology and molecular docking technology,to provide a reference for the development of Chinese medicine monomer components treating COVID-19.Methods:The active ingredients and targets of Citri Reticulatae Pericarpium were acquired by TCMSP database,and COVID-19 related targets were acquired by GeneCards database,the intersection targets of Citri Reticulatae Pericarpium and COVID-19 were acquired by Venn diagram,the protein network interaction of intersection targets was carried out in STRING database,GO enrichment and KEGG pathway enrichment analysis were carried out by data package.The core chemical components of Citri Reticulatae Pericarpium were docked with SARSCoV-23CL hydrolase and ACE2 receptor by molecular docking technology,in order to screen chemical components with better binding ability.Results:5 effective chemical constituents of Citri Reticulatae Pericarpium were obtained,and 15 intersection targets of Citri Reticulatae Pericarpium and COVID-19 were identified.PPI network mainly involved core target proteins such as MAPK3,MAPK8,CASP3,MAPK1,PTGS2,CAT,PPARG,NOS2.GO functional enrichment analysis yielded 898 biological process entries,35 cell composition entries,and 70 molecular function entries(P<0.05).In KEGG pathway analysis,139 pathways(P<0.05)were identified,mainly involving tuberculosis,hepatitis B,Kaposi's sarcoma herpesvirus infection and other pathways.Molecular docking screening results showed the active components with better binding activity to SARS-CoV-23CL hydrolase and ACE2 receptor were naringenin and orangepeptin.Conclusion:The key active ingredients(naringenin and pericarpin)screened from Citri Reticulatae Pericarpium can bind to SARS-CoV-23CL hydrolase protein(Mpro)and ACE2 receptor.Citri Reticulatae Pericarpium can inhibit pulmonary fibrosis through anti-virus,anti-inflammation,regulation of apoptosis,and immunoregulation.