Abstract
Background: We investigated the evolutionary relationships, mutations, antigenic epitopes, and structural dynamics of the receptor-binding domain (RBD) of SARS-CoV-2, Omicron and other recently evolved variants.
Methods: The RBD of SARS-CoV-2 and its Omicron, Alpha, Beta, Gamma, Delta, and Mu variants were subjected to pairwise sequence matrix evaluation, antigenic epitope prediction, and phylogenetic relationship and structural dynamics analyses.
Results: The Omicron RBD contained 13-15 amino acid mutations, of which 12 were new and three conserved with other variants. In addition, two mutations found in the Alpha, Beta, Gamma, and Mu variants were not found in the Omicron RBD. The ultrametric clustering unweighted pair group method with arithmetic mean identified Omicron as a novel monophyletic class, but the neighbor-joining method clustered Omicron with Alpha and Delta variants. In the SARS-CoV-2 RBD, five main antigenic epitopes were predicted, and these epitopes were conserved across all SARS-CoV-2 variants tested. Surprisingly, the additional mutations in the Omicron variant increased the size of the expected antigenic sites in two of these antigenic epitopes. Molecular dynamics (MD) simulations revealed higher root-mean-square deviation in the Omicron RBD, greater residue fluctuation at residues 32-42 and 140-160, and increased solvent-accessible surface area.
Conclusions: The Omicron RBD mutations indicate the variant is within a new phylogenetic class of SARS-CoV-2 and significantly impact RBD structure, conformation, and molecular dynamics. However, conserved anticipated antigenic sites may imply partial changes in receptor affinity and response to immune reactions. Omicron RBD binding with the angiotensin-converting enzyme 2 receptor was suggested to be weaker than the original SARS-CoV-2 binding in MD simulations.
Keywords: COVID-19; Omicron variant; Phylogenetics; SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2., phylogenetics, Omicron variant, 【초록키워드】 SARS-CoV-2, Mutation, mutations, variant, SARS-CoV-2 variant, Delta, molecular dynamics, omicron, angiotensin-converting enzyme 2, variants, MD simulations, Epitopes, Receptor-binding domain, SARS-CoV-2 variants, RBD, Clustering, Gamma, phylogenetics, Alpha, Omicron variant, Beta, receptor, molecular, epitope, binding, Angiotensin-converting enzyme, Amino acid, angiotensin, Phylogenetic relationship, Phylogenetic, SARS-CoV-2 RBD, Angiotensin-converting enzyme 2 receptor, surface area, Root-mean-square deviation, other variants, antigenic, residue, sequence, conformation, RBD binding, alpha and delta variants, residues, evolutionary relationships, deviation, RBD of SARS-CoV-2, FIVE, RBD mutation, fluctuation, antigenic epitopes, arithmetic mean, immune reactions, greater, tested, predicted, conserved, significantly, addition, investigated, changes in, suggested, the receptor-binding domain, expected, analyses, anticipated, antigenic epitope, antigenic site, the SARS-CoV-2, 【제목키워드】 molecular, domain,