Investigation of Obesity Gene Methylation Induced by SARS-CoV-2 Infection through Molecular Docking

Abstract

Abstract Introduction The global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been associated with a range of health complications, including the development of metabolic conditions such as obesity. Recent studies suggest that SARS-CoV-2 infection may trigger epigenetic changes in the human genome, including DNA methylation, which can influence gene expression and contribute to the development of metabolic diseases. Objective To use molecular docking simulations to identify potential interactions between viral proteins and methylation sites in the obesity gene. Methodology Data collection and processing: Genomic sequence data for SARS-CoV-2 Omicron (7QTK - SARS-CoV-2 S Omicron Spike B.1.1.529 - RBD down − 1-P2G3 Fab (Local)) were obtained from the PDB RCSB structure database. Identification of the obesity gene: The PDB RCSB structure database was used to isolate the FTO gene (4ZS2 - Structural complex of FTO/fluorescein) and the MC4R gene (6W25 - Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with SHU9119). Molecular modeling: Molecular docking simulations were carried out using AutoDock software to model the interaction between the FTO and MC4R obesity genes and proteins encoded by SARS-CoV-2 (Spike protein). DNA methylation analysis: Based on the obtained data, methylation sites in the FTO and MC4R genes were analyzed. The bisulfite sequencing technique was used to identify methylation sites. Results Docking simulations revealed potential binding interactions between viral proteins SARS-CoV-2 (Spike protein) and methylation sites in the obesity FTO gene and MC4R gene. Several structural features, including hydrophobic interactions, hydrogen bonds, and electrostatic interactions, were observed. Conclusion Molecular docking simulations identified potential interaction sites between viral proteins and methylation sites within the obesity gene, which could elucidate underlying molecular mechanisms for the relationship between SARS-CoV-2 infection and predisposition to obesity.