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Investigating the active compounds and mechanism of HuaShi XuanFei formula for prevention and treatment of COVID-19 based on network pharmacology and molecular docking analysis.

ABSTRACT: Traditional Chinese medicine (TCM) has exerted positive effects in controlling the COVID-19 pandemic. HuaShi XuanFei Formula (HSXFF) was developed to treat patients with mild and general COVID-19 in Zhejiang Province, China. The present study seeks to explore its potentially active compounds and pharmacological mechanisms against COVID-19 based on network pharmacology, molecular docking, and molecular dynamics (MD) simulation. All components of HSXFF were harvested from the pharmacology database of the TCMSP system. COVID-19-related targets were retrieved from using OMIM and GeneCards databases. The herb-compound-targets network was constructed by Cytoscape. The target protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to discover the potential key target genes and mechanism. The main active compounds of HSXFF were docked with 3C-like (3CL) protease hydrolase and angiotensin-converting enzyme 2 (ACE2). The MD simulation confirmed the binding stability of docking results. The herbs-targets network mainly contained 52 compounds and 70 corresponding targets, including key targets such as RELA, TNF, TP53, IL6, MAPK1, CXCL8, IL-1β, and MAPK14. The GO and KEGG indicated that HSXFF may be mainly acting on the IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway, etc. The molecular docking results indicated that isovitexin and procyanidin B1 showed the highest affinity with 3CL and ACE2, respectively, which were confirmed by MD simulation. These findings suggested HSXFF exerted therapeutic effects involving "multi-compounds and multi-targets." It might be working through directly inhibiting the virus, improving immune function, and reducing the inflammatory in response to anti-COVID-19. In summary, the present study would provide a valuable direction for further research of HSXFF.

SUBMITTER: Wang J

PROVIDER: S-EPMC8187140 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCoronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold‒Damp Plague Formula (CDPF) against COVID-19, which was used to treat "cold‒dampness stagnation in the lung" in Trial Versions 6 and 7 of the "Diagnosis and Treatment Protocol for COVID-19", have been demonstrated, but the effective components and their mechanism of action remain unclear.MethodsIn this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein‒protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment.ResultsThe active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs-ingredients-targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through "multi components‒multi targets‒multi pathways" at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a "CDPF-herbs-ingredients-targets-pathways-COVID-19" network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities.ConclusionsThis study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19.

Project description:Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that traditional Chinese medicine (TCM) plays a significant role for COVID-19 treatment. To explore the active components and molecular mechanism of semen armeniacae amarum treating COVID-19 by network pharmacology and molecular docking technology. The active components and potential targets of semen armeniacae amarum were retrieved from traditional Chinese medicine systems pharmacology (TCMSP) database. Coronavirus disease 2019-associated targets were collected in the GeneCards, TTD, OMIM and PubChem database. Compound target, compound-target pathway and medicine-ingredient-target disease networks were constructed by Cytoscape 3.8.0. Protein-protein interaction (PPI) networks were drawn using the STRING database and Cytoscape 3.8.0 software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main active components were verified by AutoDock Vina 1.1.2 software. A lipopolysaccharide (LPS)-induced lung inflammation model in Institute of Cancer Research (ICR) mice was constructed and treated with amygdalin to confirm effects of amygdalin on lung inflammation and its underlying mechanisms by western blot analyses and immunofluorescence. The network analysis revealed that nine key, active components regulated eight targets (Proto-oncogene tyrosine-protein kinase SRC (SRC), interleukin 6 (IL6), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), HRAS proto-oncogene (HRAS), caspase-3 (CASP3)). Gene ontology and KEGG enrichment analysis suggested that semen armeniacae amarum plays a role in COVID-19 by modulating 94 biological processes, 13 molecular functions, 15 cellular components and 80 potential pathways. Molecular docking indicated that amygdalin had better binding activity to key targets such as IL6, SRC, MAPK3, SARS coronavirus-2 3C-like protease (SARS-CoV-2 3CLpro) and SARS-CoV-2 angiotensin converting enzyme II (ACE2). Experimental validation revealed that the lung pathological injury and inflammatory injury were significantly increased in the model group and were improved in the amygdalin group. Amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR and VEGFA to involve in PI3K-Akt signalling pathway, VEGF signalling pathway and MAPK signalling pathway. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.

Project description:BackgroundLegg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments.MethodsIL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot.ResultsIt was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A.ConclusionThis study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.

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Investigating the active compounds and mechanism of HuaShi XuanFei formula for prevention and treatment of COVID-19 based on network pharmacology and molecular docking analysis.

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