Repurposing of statins: An in silico approach aimed at inflammation resolution pathways

Abstract

The study was performed to evaluate the in silico binding ability of different statins against the enzymes involved in inflammation resolution pathways to enlighten the role of statins in resolution of inflammation and as a goal to repurpose statins as inflammation resolution drugs. The protein structures of four enzymes involved in the synthesis of Specialized Pro Resolving Mediators (SPMs) viz., 12-lipoxygenase (12-LoX), 15-lipoxygenase (15-LoX), 5-lipoxygenase (5-LoX) and Aspirin acetylated cycloxygenase-2 (CoX-2) were retrieved from PDB and were used as receptors. Statins such as Atorvastatin, Simvastatin, Lovastatin, Rosuvastatin, Fluvastatin, Pravastatin and Pitavastatin were used as ligands and their 3D structures were obtained from PubChem database for computational molecular docking. The ligand interaction analysis was performed using AutoDock Vina and Biovia Discovery studio visualizer. The statins showed better binding affinities with 15-LoX and CoX-2 than the other two enzymes, which correlated with the in vivo efficacy of statins as reported earlier. Of all the statins, Pitavastatin and Atorvastatin exhibited better binding interactions with the docked enzymes. Statins are well-known for their cholesterol-lowering effects, but findings from this study suggest they may also be repurposed to promote the resolution of inflammation, which might open-up new possibilities for preventing serious chronic diseases.