Consensus insertion/deletions and amino acid variations of all coding and noncoding regions of the SARS-CoV-2 Omicron clades, including the XBB and BQ.1 lineages.

The currently dominant Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swiftly diverged into clades. To predict the probable impact of these clades, the consensus insertions/deletions (indels) and amino acid substitutions of the whole genome of clades were compared with the original SARS-CoV-2 strain. The evolutionary history of representatives of clades and lineages was inferred using the maximum-likelihood method and tested using the bootstrap method. The indels and polymorphic amino acids were found to be either clade-specific or shared among clades. The 21K clade has unique indels and substitutions, which probably represent reverted indels/substitutions. Three variations that appear to be associated with SARS-CoV-2 attenuation in the Omicron clades included a deletion in the nucleocapsid gene, a deletion in the 3'untranslated region, and a truncation in open reading frame 8. Phylogenetic analysis showed that the Omicron clades and lineages form three separate clusters.

Whole-Genome Comparison of Representatives of All Variants of SARS-CoV-2, Including Subvariant BA.2 and the GKA Clade

Since its discovery at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into many variants, including the subvariant BA.2 and the GKA clade. Genomic clarification is needed for better management of the current pandemic as well as the possible reemergence of novel variants. The sequence of the reference genome Wuhan-Hu-1 and approximately 20 representatives of each variant were downloaded from GenBank and GISAID. Two representatives with no track of in-definitive nucleotides were selected. The sequences were aligned using muscle. The location of insertion/deletion (indel) in the genome was mapped following the open reading frame (ORF) of Wuhan-Hu-1. The phylogeny of the spike protein coding region was constructed using the maximum likelihood method. Amino acid substitutions in all ORFs were analyzed separately. There are two indel sites in ORF1AB, eight in spike, and one each in ORF3A, matrix (MA), nucleoprotein (NP), and the 3′-untranslated regions (3′UTR). Some indel sites and residues/substitutions are not unique, and some are variant-specific. The phylogeny shows that Omicron, Deltacron, and BA2 are clustered together and separated from other variants with 100% bootstrap support. In conclusion, whole-genome comparison of representatives of all variants revealed indel patterns that are specific to SARS-CoV-2 variants or subvariants. Polymorphic amino acid comparison across all coding regions also showed amino acid residues shared by specific groups of variants. Finally, the higher transmissibility of BA.2 might be due at least in part to the 48 nucleotide deletions in the 3′UTR, while the seem-to-be extinction of GKA clade is due to the lack of genetic advantages as a consequence of amino acid substitutions in various genes.

Whole-Genome Comparison of Representatives of All Variants of SARS-CoV-2, Including Subvariant BA.2 and the GKA Clade.

Since its discovery at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into many variants, including the subvariant BA.2 and the GKA clade. Genomic clarification is needed for better management of the current pandemic as well as the possible reemergence of novel variants. The sequence of the reference genome Wuhan-Hu-1 and approximately 20 representatives of each variant were downloaded from GenBank and GISAID. Two representatives with no track of in-definitive nucleotides were selected. The sequences were aligned using muscle. The location of insertion/deletion (indel) in the genome was mapped following the open reading frame (ORF) of Wuhan-Hu-1. The phylogeny of the spike protein coding region was constructed using the maximum likelihood method. Amino acid substitutions in all ORFs were analyzed separately. There are two indel sites in ORF1AB, eight in spike, and one each in ORF3A, matrix (MA), nucleoprotein (NP), and the 3'-untranslated regions (3'UTR). Some indel sites and residues/substitutions are not unique, and some are variant-specific. The phylogeny shows that Omicron, Deltacron, and BA2 are clustered together and separated from other variants with 100% bootstrap support. In conclusion, whole-genome comparison of representatives of all variants revealed indel patterns that are specific to SARS-CoV-2 variants or subvariants. Polymorphic amino acid comparison across all coding regions also showed amino acid residues shared by specific groups of variants. Finally, the higher transmissibility of BA.2 might be due at least in part to the 48 nucleotide deletions in the 3'UTR, while the seem-to-be extinction of GKA clade is due to the lack of genetic advantages as a consequence of amino acid substitutions in various genes.

Annotating Spike Protein Polymorphic Amino Acids of Variants of SARS-CoV-2, Including Omicron.

The prolonged global spread and community transmission of severe acute respiratory syndrome virus 2 (SARS-CoV-2) has led to the emergence of variants and brought questions regarding disease severity and vaccine effectiveness. We conducted simple bioinformatics on the spike gene of a representative of each variant. The data show that a number of polymorphic amino acids are located mostly on the amino-terminal side of the S1/S2 cleavage site. The Omicron variant diverges from the others, with the highest number of amino acid substitutions, including the receptor-binding site (RBS), epitopes, S1/S2 cleavage site, fusion peptide, and heptad repeat 1. The current sharp global increase in the frequency of the Omicron genome constitutes evidence of its high community transmissibility. In conclusion, the proposed guideline could give an immediate insight of the probable biological nature of any variant of SARS-Cov-2. As the Omicron diverged the farthest from the original pandemic strain, Wuhan-Hu-1, we expect different epidemiological and clinical patterns of Omicron cases. On vaccine efficacy, slight changes in some epitopes while others are conserved should not lead to a significant reduction in the effectiveness of an approved vaccine.