Background:To explore the effective chemical constituents of Feiduqing formula for prevention and treatment of coronavirus disease 2019(COVID-19).Methods:The compounds and action targets of twelve herbal medicines in ...Background:To explore the effective chemical constituents of Feiduqing formula for prevention and treatment of coronavirus disease 2019(COVID-19).Methods:The compounds and action targets of twelve herbal medicines in Feiduqing formula were collected via Traditional Chinese Medicine Systems Pharmacology Database and Analytic Platform.The genes corresponding to the targets were queried through the UniProt database.The“herbal medicine-ingredient-target”network was established by Cytoscape software.The Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed by Database for Annotation,Visualization and Integrated Discovery.Molecular docking was used to analyze the binding force of core active compounds of Feiduqing formula with PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and angiotensin converting enzyme II(ACE2).Results:The“herbal medicine-ingredient-target”network included 434 nodes and 1948 edges,including 222 components such as quercetin,kaempferol,luteolin,etc.The key targets are PTGS2,HSP90AA1,PTGS1,ESR1,AR,NOS2,etc.Gene Ontology function enrichment analysis revealed 2530 items,including RNA polymerase II-specific,response to oxidative stress,transcription factor activity,etc.Kyoto Encyclopedia of Genes and Genomes pathway enrichment screened 169 signal pathways,including Human cytomegalovirus infection,Kaposi sarcoma-associated herpesvirus infection,Hepatitis B,Hepatitis C,IL-17,TNF,etc.The results of molecular docking showed that quercetin,luteolin,β-sitosterol,stigmasterol and other core active compounds have a certain degree of affinity with PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and ACE2.Conclusion:The active compounds of Feiduqing formula may have a therapeutic effect on COVID-19 pneumonia through the action on PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and ACE2,and regulating many signaling pathways.展开更多
采用网络药理学和分子对接法探究六堡茶干预COVID-19的物质基础和作用机制。通过文献与中药系统药理数据库和分析平台(TCMSP)等数据库,检索得到六堡茶的化学成分并对其进行筛选得到六堡茶活性成分及对应靶标,并将对应靶标导入Uniprot数...采用网络药理学和分子对接法探究六堡茶干预COVID-19的物质基础和作用机制。通过文献与中药系统药理数据库和分析平台(TCMSP)等数据库,检索得到六堡茶的化学成分并对其进行筛选得到六堡茶活性成分及对应靶标,并将对应靶标导入Uniprot数据库中进行基因名的校正,运用Cytoscape 3.7.1软件构建"六堡茶-成分-靶标"网络。通过GeneCards数据库对COVID-19疾病靶点进行预测。将六堡茶与疾病的靶标进行映射,采用STRING数据库分析靶标蛋白的互作关系,从中筛选出核心靶标并运用DAVID等数据库对核心靶标进行GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)通路富集分析。最后将筛选出来的活性成分与受体蛋白SARS-CoV-2 3CL水解酶(Mpro)进行分子对接。筛选得到6种六堡茶活性成分,分别是(+)-儿茶素、(-)-表没食子儿茶素没食子酸酯(EGCG)、α-菠甾醇、(-)-儿茶素没食子酸酯、角鲨烯和氯化天竺葵素,对应作用靶标156个。其中与COVID-19的共同靶标112个,核心靶标38个。GO富集分析(P <0.01)主要涉及脂多糖、细胞对缺氧的反应等。KEGG通路富集分析得到六堡茶干预COVID-19相关的HIF-1、IL-17、T细胞受体等信号通路。分子对接结果显示六堡茶中的6种主要化学成分可分别与受体蛋白Mpro结合较好,且结合能与现有报道推荐的临床使用化学药相近。六堡茶中的核心化学成分(+)-儿茶素、(-)-表没食子儿茶素没食子酸酯、α-菠甾醇、(-)-儿茶素没食子酸酯、角鲨烯、氯化天竺葵素与Mpro结合并通过MAPK1、TNF等炎症和免疫相关的靶标介导HIF-1、IL-17、T细胞受体等信号通路发挥干预COVID-19的功效。实验进一步对结合能较低的EGCG进行了Mpro的活力测定,发现IC50为3.4μmol/L,证实EGCG对Mpro有一定的抑制效果。展开更多
Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin co...Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin converting enzymeⅡ(ACE2)as receptors,using computer virtual screening technique,so as to provide a basis for combination forecasting.Methods:The molecular docking of CHM with the SARS-Cov-23 CL hydrolase and the ACE2 converting enzyme,which were taken as the targets,was achieved by the Autodock Vina software.The CHM monomers acting on 3 CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,the active ingredients were selected,and the key CHMs and compounds were speculated.Based on the perspective of network pharmacology,the chemical-target network was constructed,and the functional enrichment analysis of gene ontology and the pathway enrichment analysis of Kyoto encyclopedia of genes and genomes were carried out by DAVID to speculate about the mechanism of action of the core drug pairs.Results:There are6 small molecule compounds that have the optimal binding energy with the two target proteins.Among 238 potential anti-COVID-19 herbs screened in total,16 kinds of CHM containing the most active ingredients,and5 candidate anti-COVID-19 herbs that had been used in high frequency,as well as a core drug pair,namely,Forsythiae Fructus-Lonicerae Japonicae Flos were selected.Conclusion:The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3 CLpro and ACE2,and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target,and plays the role of anti-COVID-19 pneumonia in multi-pathway.展开更多
目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Anal...目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过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)、PubChem数据库、生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM)及SwissTarget Prediction平台查询香连片活性成分及其对应的靶点基因;根据大于2倍中位数的节点度值(degree)为条件,筛选香连片关键活性成分,并运用Cytoscape 3.6.1软件绘制关键活性成分-对应靶点网络;通过GeneCards及PHARMGKB疾病数据库,以"coronavirus pneumonia"、"COVID-19"及"SARS-CoV-2"为关键词进行检索疾病靶点基因。运用Cytoscape 3.6.1软件进行交集,得到共同靶点并构建成分-靶点-疾病网络图;通过STRING网站对共同靶点构建蛋白相互作用(Protein Protein interaction, PPI)网络,通过DAVID数据库对共同靶点进行基因本位(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析;利用CB-Dock网站对筛选出的活性成分及抗病毒化药和SARS-CoV-2 3CL水解酶及血管紧张素转化酶Ⅱ (angiotensin converting enzyme Ⅱ, ACE2)进行分子对接。结果:香连片共得到41个活性成分,其中16个关键活性成分,并与疾病靶点相交得到24个共同靶点;GO功能富集得到分子功能(molecular function, MF)、细胞组分(cellular component, CC)及其所参与的生物过程(biological process, BP)分别为125条、16条及24条;KEGG富集得到94条通路,其通路多与免疫反应和炎症反应有关,主要有PI3K-Akt、Ras、HIF-1、MAPK、NF-kB以及TNF等信号通路;分子对接得出黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱及豆甾醇等多种成分与SARS-CoV-2 3CL水解酶及ACE2的对接亲和力均强于2种临床化学药物(阿比多尔及利巴韦林)。结论:香连片多是通过作用于MAPK家族、IL1B、NFKB1、CASP3、CCL5、TNF等靶点因子来调节PI3K-Akt、MAPK、NF-kB及TNF等炎症免疫通路,以多成分、多靶点、多途径参与COVID-19的多种生理过程,从而对COVID-19有一定治疗作用;在中药成分上,黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱、豆甾醇、吴茱萸酰胺类成分等可以很好作用于COVID-19治疗中涉及到的2种关键酶(SARS-CoV-2 3CL水解酶及ACE2),故这几种中药单体成分有作为治疗COVID-19的新药潜能。展开更多
基金Key Projects in Xianning science and technology project (No.2020SFYF01)Youth Talent Project of Health Commission of Hubei Province (No.ZY2021Q026).
文摘Background:To explore the effective chemical constituents of Feiduqing formula for prevention and treatment of coronavirus disease 2019(COVID-19).Methods:The compounds and action targets of twelve herbal medicines in Feiduqing formula were collected via Traditional Chinese Medicine Systems Pharmacology Database and Analytic Platform.The genes corresponding to the targets were queried through the UniProt database.The“herbal medicine-ingredient-target”network was established by Cytoscape software.The Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed by Database for Annotation,Visualization and Integrated Discovery.Molecular docking was used to analyze the binding force of core active compounds of Feiduqing formula with PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and angiotensin converting enzyme II(ACE2).Results:The“herbal medicine-ingredient-target”network included 434 nodes and 1948 edges,including 222 components such as quercetin,kaempferol,luteolin,etc.The key targets are PTGS2,HSP90AA1,PTGS1,ESR1,AR,NOS2,etc.Gene Ontology function enrichment analysis revealed 2530 items,including RNA polymerase II-specific,response to oxidative stress,transcription factor activity,etc.Kyoto Encyclopedia of Genes and Genomes pathway enrichment screened 169 signal pathways,including Human cytomegalovirus infection,Kaposi sarcoma-associated herpesvirus infection,Hepatitis B,Hepatitis C,IL-17,TNF,etc.The results of molecular docking showed that quercetin,luteolin,β-sitosterol,stigmasterol and other core active compounds have a certain degree of affinity with PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and ACE2.Conclusion:The active compounds of Feiduqing formula may have a therapeutic effect on COVID-19 pneumonia through the action on PTGS2,HSP90AA1,SARS-CoV-23CL hydrolase and ACE2,and regulating many signaling pathways.
文摘采用网络药理学和分子对接法探究六堡茶干预COVID-19的物质基础和作用机制。通过文献与中药系统药理数据库和分析平台(TCMSP)等数据库,检索得到六堡茶的化学成分并对其进行筛选得到六堡茶活性成分及对应靶标,并将对应靶标导入Uniprot数据库中进行基因名的校正,运用Cytoscape 3.7.1软件构建"六堡茶-成分-靶标"网络。通过GeneCards数据库对COVID-19疾病靶点进行预测。将六堡茶与疾病的靶标进行映射,采用STRING数据库分析靶标蛋白的互作关系,从中筛选出核心靶标并运用DAVID等数据库对核心靶标进行GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)通路富集分析。最后将筛选出来的活性成分与受体蛋白SARS-CoV-2 3CL水解酶(Mpro)进行分子对接。筛选得到6种六堡茶活性成分,分别是(+)-儿茶素、(-)-表没食子儿茶素没食子酸酯(EGCG)、α-菠甾醇、(-)-儿茶素没食子酸酯、角鲨烯和氯化天竺葵素,对应作用靶标156个。其中与COVID-19的共同靶标112个,核心靶标38个。GO富集分析(P <0.01)主要涉及脂多糖、细胞对缺氧的反应等。KEGG通路富集分析得到六堡茶干预COVID-19相关的HIF-1、IL-17、T细胞受体等信号通路。分子对接结果显示六堡茶中的6种主要化学成分可分别与受体蛋白Mpro结合较好,且结合能与现有报道推荐的临床使用化学药相近。六堡茶中的核心化学成分(+)-儿茶素、(-)-表没食子儿茶素没食子酸酯、α-菠甾醇、(-)-儿茶素没食子酸酯、角鲨烯、氯化天竺葵素与Mpro结合并通过MAPK1、TNF等炎症和免疫相关的靶标介导HIF-1、IL-17、T细胞受体等信号通路发挥干预COVID-19的功效。实验进一步对结合能较低的EGCG进行了Mpro的活力测定,发现IC50为3.4μmol/L,证实EGCG对Mpro有一定的抑制效果。
基金Supported by the Fundamental Research Funds for the Central Central University,Scientific Research Project on Prevention and Treatment Emergency in Novel Coronavirus(No.20720200034)。
文摘Objective:To seek potential Chinese herbal medicine(CHM)for the treatment of coronavirus disease 2019(COVID-19)through the molecular docking of the medicine with SARS-CoV-23 CL hydrolytic enzyme and the angiotensin converting enzymeⅡ(ACE2)as receptors,using computer virtual screening technique,so as to provide a basis for combination forecasting.Methods:The molecular docking of CHM with the SARS-Cov-23 CL hydrolase and the ACE2 converting enzyme,which were taken as the targets,was achieved by the Autodock Vina software.The CHM monomers acting on 3 CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,the active ingredients were selected,and the key CHMs and compounds were speculated.Based on the perspective of network pharmacology,the chemical-target network was constructed,and the functional enrichment analysis of gene ontology and the pathway enrichment analysis of Kyoto encyclopedia of genes and genomes were carried out by DAVID to speculate about the mechanism of action of the core drug pairs.Results:There are6 small molecule compounds that have the optimal binding energy with the two target proteins.Among 238 potential anti-COVID-19 herbs screened in total,16 kinds of CHM containing the most active ingredients,and5 candidate anti-COVID-19 herbs that had been used in high frequency,as well as a core drug pair,namely,Forsythiae Fructus-Lonicerae Japonicae Flos were selected.Conclusion:The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3 CLpro and ACE2,and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target,and plays the role of anti-COVID-19 pneumonia in multi-pathway.
文摘目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过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)、PubChem数据库、生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM)及SwissTarget Prediction平台查询香连片活性成分及其对应的靶点基因;根据大于2倍中位数的节点度值(degree)为条件,筛选香连片关键活性成分,并运用Cytoscape 3.6.1软件绘制关键活性成分-对应靶点网络;通过GeneCards及PHARMGKB疾病数据库,以"coronavirus pneumonia"、"COVID-19"及"SARS-CoV-2"为关键词进行检索疾病靶点基因。运用Cytoscape 3.6.1软件进行交集,得到共同靶点并构建成分-靶点-疾病网络图;通过STRING网站对共同靶点构建蛋白相互作用(Protein Protein interaction, PPI)网络,通过DAVID数据库对共同靶点进行基因本位(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析;利用CB-Dock网站对筛选出的活性成分及抗病毒化药和SARS-CoV-2 3CL水解酶及血管紧张素转化酶Ⅱ (angiotensin converting enzyme Ⅱ, ACE2)进行分子对接。结果:香连片共得到41个活性成分,其中16个关键活性成分,并与疾病靶点相交得到24个共同靶点;GO功能富集得到分子功能(molecular function, MF)、细胞组分(cellular component, CC)及其所参与的生物过程(biological process, BP)分别为125条、16条及24条;KEGG富集得到94条通路,其通路多与免疫反应和炎症反应有关,主要有PI3K-Akt、Ras、HIF-1、MAPK、NF-kB以及TNF等信号通路;分子对接得出黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱及豆甾醇等多种成分与SARS-CoV-2 3CL水解酶及ACE2的对接亲和力均强于2种临床化学药物(阿比多尔及利巴韦林)。结论:香连片多是通过作用于MAPK家族、IL1B、NFKB1、CASP3、CCL5、TNF等靶点因子来调节PI3K-Akt、MAPK、NF-kB及TNF等炎症免疫通路,以多成分、多靶点、多途径参与COVID-19的多种生理过程,从而对COVID-19有一定治疗作用;在中药成分上,黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱、豆甾醇、吴茱萸酰胺类成分等可以很好作用于COVID-19治疗中涉及到的2种关键酶(SARS-CoV-2 3CL水解酶及ACE2),故这几种中药单体成分有作为治疗COVID-19的新药潜能。
