Bee Venom as a Source of Anti-Angiogenic Agents: A Computational Study

Angiogenesis, the formation of new blood vessels, is a fundamental process in tumor development, progression, and metastasis, making it a critical target in modern cancer therapy. Among natural bioactive compounds, animal venoms have emerged as a rich source of pharmacologically active peptides with potential anti-angiogenic effects. In this in silico study, we explored the therapeutic potential of bee venom peptides, focusing particularly on melittin and tertiapin, as inhibitors of tumor-induced angiogenesis. Using molecular docking techniques, these peptides were evaluated for their binding affinity toward key angiogenesis-related receptors, including platelet-derived growth factor receptor alpha (PDGFR-α), vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), and integrin αvβ3. Both melittin and tertiapin exhibited strong and specific binding affinities, with melittin showing notable interaction with PDGFR-α and tertiapin demonstrating a high affinity for integrin αvβ3. Molecular dynamics simulations further confirmed the stability and integrity of these peptide–receptor complexes over time, suggesting the potential for sustained biological activity. Additionally, functional enrichment analysis using the Reactome database revealed significant modulation of angiogenesis-related pathways, particularly those involved in cell migration and vascular remodeling. These findings highlight the potential of bee venom peptides as natural, targeted modulators of angiogenesis and support their further development as candidates for anti-cancer drug discovery.