Conserved SARS-CoV-2 Viral Peptides as Potential Prophylactic and Therapeutic Targets

Background: The ongoing evolution of SARS-CoV-2, especially the emergence of heavily mutated variants like Omicron and its sub-lineages, has resulted in antigenic drift that diminishes the effectiveness of current first-generation vaccines, diagnostic tests, and treatments. This study employed a comprehensive immuno-informatics approach to identify highly conserved protein sequences from SARS-CoV-2 isolates reported in India. 1,33,154 complete protein sequences retrieved from the GISAID database between September 2021 and March 2023 were analysed. Results: The analysis revealed a total of 62,94,995 mutations, which include 66,861 unique mutations. Sequences comprising at least eight consecutive amino acids with mutation frequencies below 0.1% were considered conserved regions. This analysis identified 270 conserved sequences across both structural and non-structural proteins. Of these, 73 sequences were found to be antigenic and non-allergenic and were mapped onto their respective crystal structure of proteins to evaluate their functional relevance. Many conserved sequences overlapped with the known functionally significant epitopes conserved across SARS-CoV-2 variants, underscoring their importance. Conclusions: The identified conserved sequences offer valuable targets for developing variant-resilient peptide-based diagnostics, monoclonal antibody therapeutics, and multi-epitope peptide vaccines. This study provides a curated collection of conserved SARS-CoV-2 protein regions identified from Indian clinical isolates and emphasises their potential for diagnostic and therapeutic applications. These findings may contribute to developing universal, variant-proof strategies for SARS-CoV-2 detection, prevention, and treatment.