Our study focuses on free energy calculations of SARS-CoV-2 spike protein receptor binding motives (RBMs) from wild type and variants of concern (VOCs), with emphasis on SARS-CoV-2 Omicron. Our computational analysis underlines the occurrence of positive selection processes that specify Omicron host adaption and bring changes on the molecular level into context with clinically relevant observations. Our free energy calculation studies regarding the interaction of Omicron’s RBM with human angiotensin converting enzyme 2 (hACE2) indicate weaker binding to the receptor than Alpha’s or Delta’s RBMs. Upon weaker binding, fewer viruses are predicted to be generated in time per infected cell, resulting in a delayed induction of danger signals as a trade-off. Along with delayed immunogenicity and pathogenicity, more viruses may be produced in the upper respiratory tract, explaining enhanced transmissibility. Since in interdependence on the human leukocyte antigen type (HLA type), more SARS-CoV-2 Omicron viruses are assumed to be required to initiate inflammatory immune responses, and because of pre-existing partial immunity through previous infections and/or vaccinations, which mostly guard the lower respiratory tract, overall disease severity is expected to be reduced.
【저자키워드】 disease severity, Computational biology, Spike protein, Receptor binding domain, Transmissibility, SARS-CoV-2 Omicron, receptor interaction, 【초록키워드】 viruses, SARS-CoV-2, Positive selection, Infection, human leukocyte antigen, variants of concern, omicron, virus, angiotensin converting enzyme, variants, Free energy calculation, Spike protein, hACE2, free energy, Antigen, Free energy calculations, immune responses, SARS-CoV-2 spike protein, VOCs, receptor, molecular, respiratory, pathogenicity, change, upper respiratory tract, wild type, binding, Interaction, Vaccinations, angiotensin, Receptor binding, Lower respiratory tract, danger signal, leukocyte, partial immunity, enzyme, human angiotensin converting enzyme 2, infected cell, trade-off, computational analysis, danger signals, HLA type, inflammatory immune responses, Host, Occurrence, produced, resulting, predicted, clinically, required, reduced, expected, assumed, RBM, 【제목키워드】 response, energy, calculation, Free,