摘要
目的利用中药网络药理学和分子对接技术,探讨清瘟汤作用靶标与新型冠状病毒(SARS-CoV-2)之间的关联以及多成分、多靶标的治疗机制。方法通过建立化学成分、靶点,筛选主要活性成分和靶标,用Cytoscape软件构建和分析网络,使用String对靶标进行GO及KEGG功能富集分析,采用Autodock软件对“清瘟汤”(QWT)主要活性成分与SARS-CoV-2的3C类似蛋白酶(3CLpro)和血管紧张素转换酶2(ACE2)蛋白进行分子对接。结果QWT中共有172个活性成分涉及480个靶标,其中大多数中药归胃经、肺经和脾经,27个活性成分(琥珀酸、香豆素、γ-氨基丁酸、谷氨酰胺、槲皮素、山柰酚、脯氨酸、赖氨酸、木犀草素、色氨酸、L-缬氨酸、胆碱、芹菜素、β-谷固醇、苯丙氨酸、丙氨酸、水杨酸、DL-缬氨酸、羽扇豆酚、腺苷、谷氨酸、熊果酸、大黄素、异鼠李素、黄豆苷元、柠檬酸、阿魏酸)与靶标关系最密切;QWT关键靶点涉及CASP3,CYP1A1,JUN,TP53,HMOX1,ICAM1,FOS,PPARG,CXCR4,SRC,TYR,B2M,MMP9,RPS27A,PSMD3,NPEPPS,CNDP2,TNF,AKT1,APP,NPY1R,CTSS,PTGER3,GGCT,UBB,HLA-A,PTGS2,CXCL8,FUM,PSMC4等,重要靶标富集在感染性疾病、肺部疾病和免疫性疾病三大类疾病通路上,GO分类和KEGG通路富集主要调控抗炎、免疫、血管生成、钙通道等相关。分子对接结果显示,槲皮素、芹菜素、熊果酸、异鼠李素、羽扇豆酚与3CLpro和ACE2蛋白具有一定的亲和力。结论QWT中的活性化合物主要作用于CASP3,CYP1A1,JUN,TP53,HMOX1等靶点,其中有5种化合物可与SARS-CoV-2的2种主要蛋白进行分子对接,QWT总体通过调节多条信号通路,从而可能产生抗SARS-CoV-2作用。
Objective To investigate the relationship between the action target of Qingwen Decoction and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the therapeutic mechanism of its multi-component and multi-target based on network pharmacology and molecular docking technology.Methods The main active components and targets were screened by establishing a database of chemical components and targets,the network was constructed and analyzed by using the Cytoscape software,the GO and KEGG functional enrichment analysis of targets was carried out by String,the molecular docking of the main active components of Qingwen Decoction and the 3C-like protease(3CLpro)and angiotensin-converting enzyme 2(ACE2)protein of SARS-CoV-2 were carried out by Autodock software.Results There were 172 active components and 480 targets in Qingwen Decoction and most of them belonged to the stomach,lung and spleen meridian.Totally 27 active components(succinic acid,coumarin,gamma-aminobutyric acid,glutamine,quercetin,kaempferol,prolinum,L-lysine,luteolin,tryptophane,L-valine,choline,apigenin,beta-sitosterol,phenylalanine,a lanine,salicylic acid,DL-valine,lupeol,adenosine,glutamate,ursolic acid,emodin,isorhamnetin,daidzein,citric acid,ferulic acid)were most closely related to the targets.The key targets of Qingwen Decoction involved CASP3,CYP1A1,JUN,TP53,HMOX1,ICAM1,FOS,PPARG,CXCR4,SRC,TYR,B2M,MMP9,RPS27A,PSMD3,NPEPPS,CNDP2,TNF,AKT1,APP,NPY1R,CTSS,PTGER3,GGCT,UBB,HLA-A,PTGS2,CXCL8,FUM,PSMC4 and so on.The important targets are enriched in the three major disease pathways of infectious disease,lung disease and immune disease,and the GO classification and KEGG pathway enrichment were mainly regulated anti-inflammatory,immune,angiogenesis,calcium channels and so on.The results of molecular docking showed that quercetin,apigenin,ursolic acid,isorhamnetin and lupeol had affinity with 3CLpro and ACE2 protein.Conclusion The active components in Qingwen Decoction mainly act on targets such as CASP3,CYP1A1,JUN,TP53 and HMOX1.Among them,five components can be molecularly docked with two main proteins of SARS-CoV-2.Qingwen Decoction may have anti-SARS-CoV-2 by regulating multiple signal pathways.
作者
马诗瑜
方洁
卞晓岚
杨铭
郑岚
郑林
MA Shiyu;FANG Jie;BIAN Xiaolan;YANG Ming;ZHENG Lan;ZHENG Lin(Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China 200023;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China 200032;Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China 200003)
出处
《中国药业》
CAS
2020年第7期1-9,共9页
China Pharmaceuticals
基金
上海交通大学医学院“临床药学创新研究院”重点专项建设项目[CXYJY2019MS004]
2020年度上海交通大学医学院新型冠状病毒感染肺炎抗疫相关药事管理与合理用药研究专项[JDYX2020KYZX010]
2020年度上海交通大学医学院新型冠状病毒感染肺炎抗疫相关药事管理与合理用药研究专项[JDYX2020KYZX011]
上海中医药大学附属龙华医院防治新型冠状病毒(COVID-19)应急科研攻关项目。
关键词
新型冠状病毒
分子对接技术
清瘟汤
网络药理学
抗病毒
作用机制
severe acute respiratory syndrome coronavirus 2
molecular docking technology
Qingwen Decoction
network pharmacology
antivirus
mechanism of action
