Deciphering SARS-CoV-2 EG.5: Advanced Molecular Docking and In-Silico Insights into Structural and Genetic Variations of Spike Protein Subvariants

The SARS-CoV-2 EG.5 variant carries mutations that may influence transmissibility, disease severity, and immune escape. Despite widespread population immunity, continued surveillance remains essential. In this study, density functional theory (DFT) calculations at the B3LYP/6-311G(d,p) level were employed to optimize molecular geometries and examine frontier molecular orbitals (HOMO–LUMO), providing supportive insights into electronic properties such as reactivity and stability. Selected quantum chemical descriptors—including dipole moment, electronegativity, hardness/softness, and electrophilicity—were analyzed, while molecular electrostatic potential (MEP) maps illustrated electron density distribution. These calculations are used here to complement, rather than establish, biological mechanisms related to Spike–ACE2 interactions. In parallel, molecular docking was performed to comparatively assess interaction tendencies between Spike protein variants and ACE2. The docking outputs are interpreted qualitatively as relative interaction scores, not as binding free energies or experimentally validated affinities. EG.5 showed comparatively higher interaction scores, with similar trends observed for Delta and Wuhan-1 variants, whereas Omicron displayed relatively lower interaction scores. Overall, these findings provide a comparative computational perspective on variant-dependent interaction patterns, offering supportive insights that may inform further experimental and epidemiological investigations.