Atomic-scale Quantum Chemical Calculation of Omicron Mutations Near Cleavage Sites of the Spike Protein

ABSTRACT The attachment of the Spike-protein in SARS-CoV-2 to host cells and the initiation of viral invasion are two critical processes in the viral infection and transmission processes in which the presence of unique furin (S1/S2) and TMPRSS2 (S2’) cleavage sites play a pivotal role. In this study, we provide detailed analysis of the impact of the BA.1 Omicron variant mutations, vicinal to these two cleavage sites using a novel computational method based on Amino acid – amino acid bond pair unit (AABPU), a specific protein structural unit in 3D as a proxy for quantifying the atomic interaction. We have identified several key features related to the electronic structure as well as bonding of the Omicron mutations near the cleavage sites that significantly increase the size of the relevant AABPUs and the fraction of the positive partial charge. These results of the ultra-large-scale quantum calculations enable us to conjecture on the biological role of Omicron mutations and their specific effects on cleavage sites, as well as identify the principles that can be of some value in analyzing other new variants or subvariants.