The pharmacological mechanism and molecular details of Platycodon grandiflorum in the treatment of novel coronavirus Pneumonia(COVID-19)

Background:Novel coronavirus pneumonia(COVID-19)has developed as a pandemic of global concern.There is an urgent need to develop effective and safe therapies.Platycodon grandiflorum(PG),one of the most famous traditional Chinese herbs,may be satisfied.In this study,we explored the pharmacological mechanism of PG in the treatment of COVID-19.Method:The active compounds and potential targets were acquired from public databases.The protein-protein interaction,the Gene Ontology,and the Kyoto Encyclopedia of Genes and Genomes were determined through bioinformatics analysis.Molecular docking and molecular dynamics were performed to further verify the findings.Result:A total of 38 bioactive ingredients and 276 gene targets of PG were identified.There were 78 intersected targets of PG and COVID-19.The network analysis revealed that luteolin,Platycogenic acid A,Platycogenic acid C,Polygalacic acid,and acacetin may be candidate agents.The AKT1,VEGFA,TP53,MAPK3,TNF,IL6,CASP3,EGFR,STAT3,and CCND1 were the important potential drug targets.Gene Ontology terms are involved in biological processes,which are mainly concentrated in inorganic substances and apoptosis,etc.The Kyoto Encyclopedia of Genes and Genomes pathway was involved in several aspects,such as Virus infection and immune regulation-related pathways.Molecular docking results showed that compounds of PG are closely bound to related targets.Molecular dynamics further found that Robin,Flavplatycoside,and dimethyl 3-O-β-D-glucopyranosylplatycogenate A can maintain good stability and flexibility in the composite system.Conclusion:PG has multicomponent,multitarget,and multichannel characteristics,which can provide an important theoretical basis to treat patients with COVID-19.

Network analysis and molecular docking of the mechanism of Shengmai decoction in treating patients with severe novel coronavirus pneumonia

Background:Studies have shown that,Shengmai injection(Shengmai decoction)which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.However,the mechanism of its intervention in severe stage of COVID-19 at molecular level is still unclear.Therefore,it is necessary to further explore the mechanism of Shengmai decoction in the treatment of patients with severe COVID-19 based on network pharmacology.Methods:The Traditional Chinese Medicine Systems Pharmacology,BATMAN,UniProt databases and the published literatures which contain the reported compounds that have therapeutic effects on COVID-19 were used to screen out the active ingredients and targets of Shengmai decoction,and the“drug-active compound-target”network was constructed.The GeneCards database was used to screen out the targets of COVID-19.The protein-protein interaction network map was constructed by mapping two genes,and the network of active ingredients,targets and disease was constructed using Cytoscape software.Thereafter,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the key targets were performed using the Metascape Site Maintenance website and David databases.The Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the mapping targets were analyzed.Results:The active component-target network contained 73 main compounds and 457 targets.The first five main active components(hydroquinone,guanosine,ophiopogon C,ophiopogon B,ophiopogon D)were obtained by topological analysis of 33 common targets.Using the Matthews correlation coefficient algorithm,the key targets included albumin,tumor necrosis factor,and cyclic adenosine response element binding.Compounds in Shengmai decoction were found to have good binding effect and strong interaction with caspase-8,caspase-3,apoptosis regulator Bcl-2,tumor necrosis factor,C-C motif chemokine 3,to inhibit the inflammatory response and improve lung injury.Additionally,31 biological processes were obtained by Gene Ontology enrichment,mainly related to lipopolysaccharide response and cytokine-mediated signal pathways,and 71 biological processes were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment,mainly related to pulmonary tuberculosis,hepatitis B,and mitogen-activated protein kinase signal pathways.Conclusion:Shengmai decoction has multicomponent,multitarget and multichannel characteristics,which can provide an important theoretical basis to treat patients with severe COVID-19.