Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingr...Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.展开更多
Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we r...Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we reveal a previously unidentified function of G6PD.It,even the natural G6PD deficiency-associated mutant without the activity to maintain the normal oxPPP,can antagonize the stresses by supporting the reductive glutamine metabolism and AMPK activation,independently of the NADPH generation by the oxPPP.展开更多
基金The work was supported by The Educational Research Project for Young and Middle-aged Teachers of Fujian Provincial Department of Education(JAT190982)The Open Research Project Funding Project of Fujian University Engineering Research Center of Biochemical Pharmaceuticals and The Innovation and Entrepreneurship Training Program for College Students of Fujian Province(S202012709029).
文摘Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.
基金supporled in part by grants from the National Nature Science Foundation of China(81972567 and 81672762 to B.L.,81830087,U1602221 and 31771516 to C.C.81802671 and 81872414 to DJ.)Grant CIT&TCD20190333 from the Support Projectof High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,Tianjin Natural Science Foundation(No.18JCONJC79600)+1 种基金Project oflnnovative Research Team of Yunnan Province(2019HCO05)Yunnan Funda-mentall Pesearch Projects(12019FB112 and 202001A070018 to DJ).
文摘Dear Editor,Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the oxidative pentose phosphate pathway(oxPPP)that can generate cytosolic NADPH(Fig.1a)for biosynthesis and oxidative defence.Here,we reveal a previously unidentified function of G6PD.It,even the natural G6PD deficiency-associated mutant without the activity to maintain the normal oxPPP,can antagonize the stresses by supporting the reductive glutamine metabolism and AMPK activation,independently of the NADPH generation by the oxPPP.
