Epigenetic Targeting of Obesity Genes by the SARS-CoV-2 Spike Protein

Objective To computationally evaluate binding interactions between SARS-CoV-2 spike protein and methylation sites within obesity-associated genes FTO and MC4R using molecular docking simulations. Methods Structural data for SARS-CoV-2 Omicron variant spike protein (PDB: 7QTK), FTO gene (PDB: 4ZS2), and MC4R gene (PDB: 6W25) were retrieved from RCSB Protein Data Bank. Three-dimensional molecular structures were prepared through addition of hydrogen atoms, geometric optimization, and removal of non-essential molecules. Methylation sites within FTO and MC4R genes were designated as binding targets. AutoDock software executed molecular docking algorithms to simulate protein-gene interactions, evaluating favorable binding conformations, energetics, and molecular interaction characteristics including hydrogen bonding, hydrophobic contacts, and electrostatic forces. Structural analysis identified potential interaction sites and binding affinities between viral spike protein and obesity gene methylation regions. Results Molecular docking simulations revealed significant binding interactions between SARS-CoV-2 spike protein and methylation sites in both FTO and MC4R genes, characterized by multiple hydrophobic interactions, hydrogen bonds, and electrostatic contacts. Conclusion Computational analysis demonstrates potential molecular interactions between SARS-CoV-2 spike protein and epigenetic regulatory sites of obesity-associated genes, suggesting plausible mechanistic pathways linking viral infection to obesity predisposition through epigenetic modulation.