Fecha de publicación: -- Fuente: PubMed "apis mellifera" Eur J Med Chem. 2026 Nov 3;321(Pt 3):119478. doi: 10.1016/j.ejmech.2026.119478. Online ahead of print.ABSTRACTThe continuing emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlights the need for host-directed antiviral strategies with specific molecular mechanisms. Honeybee (Apis mellifera) venom (HBV) contains bioactive peptides with immunomodulatory and membrane-active properties, yet their effects on SARS-CoV-2 infection remain insufficiently characterized. Here, we investigated the antiviral activity and proteomic impact of whole HBV and two venom-derived peptides, apamin (APA) and tertiapin (TERT), in human angiotensin-converting enzyme 2-expressing HEK293 cells infected with SARS-CoV-2 spike-pseudotyped lentiviral particles. Cell viability and membrane integrity assays showed that HBV, APA, and TERT exerted limited cytotoxicity at the tested concentrations. In pseudovirus infectivity assays, HBV displayed the strongest inhibitory effect, reducing viral infectivity to 61.3% at 2 μg/mL, whereas APA reduced it to 73.3% at 0.5 μg/mL, and TERT showed weaker inhibitory activity. Comparative nano-liquid chromatography matrix-assisted laser desorption/ionization tandem mass spectrometry revealed treatment-associated remodelling of the host-cell proteome. A shared signature of 215 proteins across HBV-, APA-, and TERT-treated infected cells was enriched in binding and catalytic activity, translational proteins, metabolite interconversion enzymes, cytoskeletal proteins, and pathways linked to integrin, Wnt, interferon, and Janus kinase/signal transducer and activator of transcription signalling. Protein-protein interaction analysis highlighted functional clusters associated with cytoplasmic translation, viral mRNA translation, and the Sec61 translocon complex, with EFTUD2, EPRS1, and HSPA4 emerging as central hubs. HBV treatment additionally promoted immune-related and interferon-stimulated gene products, including factors involved in innate antiviral defence, cytoskeletal organization, ion transport, and membrane structural reinforcement. These findings suggest that HBV reduces SARS-CoV-2 pseudovirus infectivity through a multifactorial host-directed mechanism involving antiviral signalling, cellular architecture, and proteostasis, supporting further investigation of bee venom-derived compounds as antiviral agents.PMID:42981878 | DOI:10.1016/j.ejmech.2026.119478