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

Abstract

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.

Difference of Clinical Characteristics in Patients with Omicron and Delta Variants of SARS-CoV-2 in Beijing, China

“…This tyrosine (Y)-enriched peptide has 2 contact sites (Y449 and Y453) and is known as the NF9 peptide; in contrast to the Delta variant, the NF9 amino acid content of the Omicron variant remains unchanged, indicating that the NF9 peptide may lead to early activation of the immune system and the release of efficient cytokine, resulting in a faster immunological response and a reduction in SARS-CoV-2 pathogenicity. [13] In this study, the moderate patients in the Delta and Omicron variants group represented a high proportion of patients 60 years or older, suggesting that old age is still one of the risk factors. At the same The continuous normal distributed variables were described as means and standard deviations.…”

“…This tyrosine (Y)-enriched peptide has 2 contact sites (Y449 and Y453) and is known as the NF9 peptide; in contrast to the Delta variant, the NF9 amino acid content of the Omicron variant remains unchanged, indicating that the NF9 peptide may lead to early activation of the immune system and the release of efficient cytokine, resulting in a faster immunological response and a reduction in SARS-CoV-2 pathogenicity. [13]…”

Vaccination Is Associated With Shorter Time to Target Cycle Threshold Value in Patients With SARS-CoV-2 Omicron Variant

“…This study shows that the vaccinated patients had shorter TtCT than the unvaccinated ones, indicating the inactivated vaccines keep working effectively against SARS-CoV-2 Omicron variant in the Chinese population. The mutations are causing numbers of SARS-CoV-2 variants that confer escape from antibodies ( Kontopodis et al., 2022 ). There is no guarantee that the disease caused by subsequent mutations will be less severe and that the previous vaccines are still effective.…”

Unique peptide signatures of SARS-CοV-2 virus against human proteome reveal variants’ immune escape and infectiveness

“…Hence, to thoroughly map the UP-specific landscape of a proteome of interest, we have developed a novel bioinformatics tool that is based on advanced algorithms being dedicated to big-data analysis. Its engagement to deep and accurate processing of the 20.430 reviewed Homo sapiens (human) proteins led to the recognition and identification of more than 7x10 6 CrUPs, which represent the backbone of human Uniquome that is mainly described as the voluminous collection of UPs shaping the human proteome ( Kontopodis et al , 2022 and Kontopodis et al manuscript in preparation).…”

“…Furthermore, they can be used as diagnostic and antigenic peptides, and likely therapeutic targets, as well. Altogether, these CrUPs seem to represent a completely new entity of peptides capable to significantly improve our view and comprehension regarding the structuring, functioning and mapping of virus and human Uniquomes, and their proteomic “cross-talks”, towards immune escape and infectiveness ( Kontopodis et al , 2022 ).…”