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
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
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
Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicin...Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicine(TCM)has played an indispensable role in the battle against the epidemic.Many components originated from TCMs were found to inhibit the production of SARS-CoV-23C-like protease(3CLpro)and papain-like protease(PLpro),which are two promising therapeutic targets to inhibit SARS-CoV-2.This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis,which results in the characterization of 12 new flavonoids,including seven prenylated flavanones(1−7),one prenylated flavonol(8),two prenylated chalcones(9−10),one isoflavanone(11),and one isoflavan dimer(12),together with 43 known compounds(13−55).Their structures including the absolute configurations were elucidated by comprehensive analysis of MS,1D and 2D NMR data,and time-dependent density functional theory electronic circular dichroism(TDDFT ECD)calculations.Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-23CLpro with IC_(50) values of 34.89 and 19.88μmol·L^(−1),repectively while compounds 9,43 and 47 exhibited inhibitory effects against PLpro with IC_(50) values of 32.67,79.38,and 16.74μmol·L^(−1),respectively.展开更多
Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respi...Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003.CKI is known to inhibit inflammation,and its main chemical components,namely matrine and oxymatrine,can promote Th cells to recognize and eliminate viruses.In this study,network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients.The“ingredient-target”network was constructed using the Cytoscape software.The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets.Results:Sophocarpine,sophoridine,matrine,(+)-allomatrine,AIDS211310,and sophranol were the six active ingredients.After docking the active ingredients with severe acute respiratory syndrome coronavirus 23CL hydrolase and angiotensin-converting enzyme 2(ACE2),they displayed suitable affinity,which could block viral replication and its binding to ACE2.The key targets mainly involved inflammatory factors,such as interleukin-6(IL-6)and tumor necrosis factor(TNF).Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway.The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway.Conclusion:The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors.They regulate the IL-6-mediated signaling pathway,TNF signaling pathway,and steroid hormone biosynthesis,thereby initiating therapeutic responses against coronavirus disease 2019.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.
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This work was supported from the National Natural Science Foundation of China(Nos.82173696 and 21920102003)the Science and Technology Commission of Shanghai Municipality(Nos.20431900200 and 20430780300)+1 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(Nos.SIMM010110 and SIMM040302)the Sustainable Development of Precious Traditional Chinese Medicine Resources(No.2060302-2001-01).
文摘Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)had caused a global pandemic since 2019,and posed a serious threat to global health security.Traditional Chinese medicine(TCM)has played an indispensable role in the battle against the epidemic.Many components originated from TCMs were found to inhibit the production of SARS-CoV-23C-like protease(3CLpro)and papain-like protease(PLpro),which are two promising therapeutic targets to inhibit SARS-CoV-2.This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis,which results in the characterization of 12 new flavonoids,including seven prenylated flavanones(1−7),one prenylated flavonol(8),two prenylated chalcones(9−10),one isoflavanone(11),and one isoflavan dimer(12),together with 43 known compounds(13−55).Their structures including the absolute configurations were elucidated by comprehensive analysis of MS,1D and 2D NMR data,and time-dependent density functional theory electronic circular dichroism(TDDFT ECD)calculations.Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-23CLpro with IC_(50) values of 34.89 and 19.88μmol·L^(−1),repectively while compounds 9,43 and 47 exhibited inhibitory effects against PLpro with IC_(50) values of 32.67,79.38,and 16.74μmol·L^(−1),respectively.
基金Natural Science Foundation of Hebei Province(H2018201179)Youth Fund of Education Department of Hebei Province(QN2019146)Scientific Research Fund of Health Department of Hebei Province(NO:20190948).
文摘Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003.CKI is known to inhibit inflammation,and its main chemical components,namely matrine and oxymatrine,can promote Th cells to recognize and eliminate viruses.In this study,network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients.The“ingredient-target”network was constructed using the Cytoscape software.The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets.Results:Sophocarpine,sophoridine,matrine,(+)-allomatrine,AIDS211310,and sophranol were the six active ingredients.After docking the active ingredients with severe acute respiratory syndrome coronavirus 23CL hydrolase and angiotensin-converting enzyme 2(ACE2),they displayed suitable affinity,which could block viral replication and its binding to ACE2.The key targets mainly involved inflammatory factors,such as interleukin-6(IL-6)and tumor necrosis factor(TNF).Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway.The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway.Conclusion:The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors.They regulate the IL-6-mediated signaling pathway,TNF signaling pathway,and steroid hormone biosynthesis,thereby initiating therapeutic responses against coronavirus disease 2019.
