Abstract

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 STING and MAVS signaling 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. 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, IRF3, IRF7, TBK1, NF-κB, cGAS, RIG-I, and 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.

Key words: Metformin, STING, MAVS, innate immunity, molecular docking, antiviral response