Prediction of SARS-CoV-2 Omicron Variant Immunogenicity, Immune Escape and Pathogenicity, through the Analysis of Spike Protein-Specific Core Unique Peptides

The recently discovered Omicron variant of the SARS-CoV-2 coronavirus has raised a new, global, awareness. In this study, we identified the Core Unique Peptides (CrUPs) that reside exclusively in the Omicron variant of Spike protein and are absent from the human proteome, creating a new dataset of peptides named as SARS-CoV-2 CrUPs against the human proteome (C/H-CrUPs), and we analyzed their locations in comparison to the Alpha and Delta variants. In Omicron, 115 C/H-CrUPs were generated and 119 C/H-CrUPs were lost, almost four times as many compared to the other two variants. At the Receptor Binding Motif (RBM), 8 mutations were detected, resulting in the construction of 28 novel C/H-CrUPs. Most importantly, in the Omicron variant, new C/H-CrUPs carrying two or three mutant amino acids were produced, as a consequence of the accumulation of multiple mutations in the RBM. These C/H-CrUPs could not be recognized in any other viral Spike variant. Our findings indicated that the virus binding to the ACE2 receptor is facilitated by the herein identified C/H-CrUPs in contact point mutations and Spike cleavage sites, while the immunoregulatory NF9 peptide is not detectably affected. Thus, the Omicron variant could escape immune-system attack, while the strong viral binding to the ACE2 receptor leads to the highly efficient fusion of the virus to the target cell. However, the intact NF9 peptide suggests that Omicron exhibits reduced pathogenicity compared to the Delta variant.