Screening of key host targets and mechanistic assessment of berberine modulation of host responses to respiratory syncytial virus.

ObjectiveTo screen potential host targets and investigate the molecular mechanism by which berberine regulates host responses to respiratory syncytial virus infection.MethodsThe structure and potential targets of berberine were retrieved and predicted using the PubChem, Swiss Target Prediction, and Pharm Mapper databases. Respiratory syncytial virus-related targets were screened from the GeneCards and Online Mendelian Inheritance in Man databases. Intersection targets were obtained using Venny 2.1.0. A protein-protein interaction network of the intersection targets was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins, and core targets were screened by performing topological analysis using Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. Molecular docking between berberine and the core targets was conducted using PyMol and AutoDock.ResultsIn total, 299 berberine targets and 1196 respiratory syncytial virus targets were obtained, with 72 intersecting targets. Protein-protein interaction analysis identified 6 core targets, including epidermal growth factor receptor, Src, heat shock protein 90-alpha, albumin, signal transducer and activator of transcription 1, and caspase-3. Gene Ontology enrichment analysis indicated that the intersecting targets were involved in biological processes such as the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, localized in cellular components including cytosol, and possessed molecular functions such as protein kinase activity. Kyoto Encyclopedia of Genes and Genomes analysis enriched 145 signaling pathways. Molecular docking results showed that the binding energies of berberine to the 8 core targets were all lower than -5 kcal/mol, presenting strong binding affinity.ConclusionThrough network pharmacology and molecular docking, this study preliminarily suggests that berberine targets epidermal growth factor receptor, Src, heat shock protein 90-alpha, albumin, signal transducer and activator of transcription 1, and caspase-3 and regulates cell proliferation, inflammatory response, antiviral immunity, and cell apoptosis to modulate host response to respiratory syncytial virus infection. This study represents a purely bioinformatics prediction research, and its findings potentially provide a preliminary theoretical basis for elucidating the mechanism by which berberine regulates respiratory syncytial virus infection.