Akademik Veri Yönetim Sistemi
Medicine Science, cilt.14, sa.2, ss.472-481, 2025 (TRDizin)
Metformin, a widely used antidiabetic drug, has been increasingly recognized for its immunomodulatory effects, particularly in antiviral and inflammatory responses. This study investigates the potential of metformin to modulate mitochondria-mediated antiviral innate immunity through molecular docking analysis. The study focuses on key proteins within the the stimulator of interferon gene (STING) and mitochondrial antiviral-signaling (MAVS) pathways, which play a critical role in the activation of interferon responses and the production of inflammatory cytokines. Protein-protein interaction (PPI) network analysis was performed using the STRING database, and molecular docking simulations were conducted to identify potential binding regions and affinities between metformin and target proteins. 5'-adenosine monophosphate-activated protein kinase (AMPK) was used as a reference protein to compare binding interactions. Docking results revealed that metformin exhibited moderate binding affinities (-4.5 to -5.5 kcal/mol) with key immune regulators, including MAVS, STING, interferon regulatory factors 3 (IRF3), interferon regulatory factors 7 (IRF7), TANK-binding kinase 1 (TBK1), nuclear transcription factor-κB (NF-κB), cyclic GMP-AMP synthase (cGAS), Retinoic acid-inducible gene I (RIG-I ), and Melanoma Differentiation-Associated protein 5 (MDA5). Notably, metformin showed a strong interaction with AMPK (ΔG=-5.5 kcal/mol), supporting a link between its metabolic and immune-modulating effects. The ability of metformin to interact with critical components of the STING and MAVS pathways suggests that it may influence innate immune responses, particularly in viral infections and inflammatory diseases. These findings provide new insights into the immunoregulatory properties of metformin, emphasizing the need for further experimental studies to better understand its effects on inflammation.