Omicron SARS-CoV-2 Spike-1 Protein’s Decreased Binding Affinity to ?7nAChr: Implications for Autonomic Dysregulation of the Parasympathetic Nervous System and the Cholinergic Anti-Inflammatory Pathway—An In Silico Analysis

Omicron is the dominant strain of COVID-19 in United States and worldwide. Although this variant highly transmissible may evade natural immunity, vaccines, therapeutic antibodies, preclinical results animal models clinical data humans suggest omicron causes a less severe form infection. The molecular basis for attenuation virulence when compared to previous variants currently not well understood. Using protein–ligand docking simulations evaluate compare capacity SARS-CoV-2 spike-1 proteins with different bind human ?7nAChr (i.e., core receptor under control vagus nerve regulating parasympathetic nervous system cholinergic anti-inflammatory pathway), we found that 10 out 14 mutated residues on RBD B.1.1.529 (Omicron) spike, between 0 2 all variants, were present at interaction interface ?7nAChr. We also demonstrated, through protein–protein simulations, these genetic alterations cause dramatic decrease ability protein These suggest, first time, attenuated nature infection animals be attributable particular set alterations, specifically affecting binding site