Unique peptide signatures of SARS-C omicron V-2 virus against human proteome reveal variants' immune escape and infectiveness

SARS-CoV-2 pandemic has necessitated the identification of sequence areas in the viral proteome that are capable to serve as antigenic sites and treatment targets. In the present study, we have applied a novel approach for mechanistically illuminating the virus-host organism interactions, by analyzing the Unique Peptides (UPs) of the virus featured by a minimum amino acid sequence length being defined as Core Unique Peptides (CrUPs), not of the virus per se, but against the entire proteome of the host organism. This approach resulted in the identification of CrUPs of the virus itself, which could not be recognized in the host organism proteome. Thereby, we analyzed the SARS-CoV-2 proteome for identification of CrUPs against the human proteome, which have been defined as C/ H-CrUPs. We herein reveal that SARS-CoV-2 include 7.503 C/H-CrUPs, with the SPIKE_SARS2 being detected as the protein with the highest density of C/H-CrUPs. Extensive analysis has indicated that the critical P681R mutation produces new C/H-CrUPs around the R685 cleavage site, while the L452R mutation causes loss of antigenicity of the NF9 peptide and strong(er) binding of the virus to its ACE2 receptor protein. Simultaneous formation of these mutations in detrimental variants like Delta leads to the immune escape of the virus, its massive entrance into the host cell, a notable increase in virus formation, and its massive release and thus elevated infectivity of human target cells.