以C-C基序趋化因子配体2(CCL2)为受体挖掘治疗新型冠状病毒肺炎(COVID-19)潜在中药单体化合物  

Investigation of Potential Monomeric Compounds of Traditional Chinese Medicine in the Treatment of Coronavirus Disease Pneumonia(COVID-19)Based on C-C Motif Chemokine 2(CCL2)Receptor

作　　者：李乾胜 曹灿 李玲玲[2] 冯静[2] 巫晓慧 崔瑛[2,3] LI Qiansheng;CAO Can;LI Lingling;FENG Jing;WU Xiaohui;CUI Ying(Zhengzhou Hospital of Traditional Chinese Medicine,Zhengzhou 450007,China;Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;Co Construction Collaborative Innovation Center,Henan University of Traditional Chinese Medicine Respiratory Disease Prevention and Treatment Province Ministry,Zhengzhou 450000,China)

机构地区：[1]郑州市中医院,郑州450007 [2]河南中医药大学,郑州450046 [3]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,郑州450000

出　　处：《世界中医药》2021年第3期415-425,共11页World Chinese Medicine

基　　金：国家自然科学基金面上项目(81473368)。

摘　　要：目的:C-C基序趋化因子配体2(CCL2)为受体探索治疗新型冠状病毒肺炎(COVID-19)的中药单体化合物及作用机制。方法:以“C-C motif chemokine 2”为检索词在中药系统药理学分析平台(TCMSP)检索作用于CCL2受体的中药单体化合物,并收集其作用靶点。在GeneCards及OMIM数据库中以“fever”“cough”“pneumonia”“coronavirus”为检索词收集相应靶点,并添加“木瓜样蛋白酶(PLP)”“树突状细胞特异性细胞间黏附分子-3结合非整合素因子(DC-SIGN)”,合并作为COVID-19相关靶点。UniProt数据库标化靶点基因名,取中药单体化合物靶点与疾病靶点的交集。运行Cytoscape软件构建中药单体化合物-交集靶点网络,用交集靶点通过STRING数据库及Cytoscape软件构建蛋白互作(PPI)网络;借DAVID数据库进行GO功能富集、KEGG通路富集,而预测中药单体化合物治疗COVID-19的作用机制。然后将所有中药单体化合物与CCL2、新型冠状病毒(SARS-CoV-2)3CL水解酶和血管紧张素转化酶Ⅱ(ACE2)进行分子对接。结果:中药单体成分-靶点网络中包含单体成分2个,交集靶点153个,PPI网络分析显示关键靶点涉及AKT1、IL6、VEGFA等。GO功能富集所得GO条目115个,其中涉及CCL2条目有10个,KEGG通路富集所得信号通路97条,其中涉及CCL2有9条。分子对接结果显示槲皮素、汉黄芩素与CCL2、SARS-CoV-23CL水解酶和ACE2的亲和力与推荐化药相近。结论:槲皮素、汉黄芩素可与CCL2结合作用于肿瘤坏死因子信号通路、查加斯病(美国锥虫病)、甲型流感信号通路,从而可能发挥抗COVID-19的作用。Objective:To investigate the mechanism and traditional Chinese medicine monomer compounds in the treatment of COVID-19 with C-C motif chemokine 2(CCL2)as a receptor.Methods:TCMSP was used to search for the compounds of Chinese medicine monomers acting on CCL2 receptor and for collecting their targets.In GeneCards and OMIM databases,the corresponding targets were collected with the key words of“fever”,“cough”,“pneumonia”and“coronavirus”,and“papain like protease(PLP)”and“dendritic cell specific intercellular adhesion molecule-3 binding non integrin factor(DC-SIGN)”were added as COVID-19 related targets.UniProt database corrected the gene name of the targets,and took the intersection of monomer compounds and disease targets.In order to predict the interaction mechanism of the targets,we used the STRING database and the Cytoscape 3.7.2 to construct the protein interaction(PPI)network,and the DAVID database to analyze the function enrichment of GO and the enrichment of KEGG pathway.Then all traditional Chinese medicine monomer compounds were linked to CCL2,SARS-CoV-23CL hydrolase and angiotensin-converting enzymeⅡ(ACE2)for molecular docking.Results:There are 2 monomer components and 153 intersection targets in the network of monomer targets and traditional Chinese medicine.PPI network analysis showed that the key targets were AKT1,IL6,VEGFA,etc.There were 115 GO entries,10 CCL2 entries in GO functional enrichment analysis,97 signal pathways and 9 CCL2 signal pathways in KEGG pathway enrichment analysis.The results of molecular docking showed that the affinity of the recommended Chinese medicine monomers with CCL2,SARS-CoV-23CL hydrolase and ACE2 was similar to that of the recommended drugs.Conclusion:Quercetin and wogonin can combine with CCL2 to act on TNF signaling pathway,Chagas disease(American trypanosomiasis)and Influenza A signaling pathway,which may play an anti-COVID-19 role.

关 键 词：C-C基序趋化因子配体2(CCL2) 新型冠状病毒肺炎 网络药理学 分子对接 槲皮素 汉黄芩素 中药单体化合物 靶点 

分 类 号：R285[医药卫生—中药学] R242[医药卫生—中医学]