A recently identified novel epitope, which maps to the furin cleavage site, a crucial virulence factor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has shown that its corresponding antibody may be able to neutralize the virus before it enters a host cell. This study aimed to identify conserved and distinct epitopes that map to the furin cleavage site of the SARS-CoV-2 spike protein across various SARS-CoV-2 variants, focusing on the top two most frequent human leukocyte antigen (HLA) alleles across Southeast Asia. In this study, we predicted potential epitopes that map to the furin cleavage site within the immune epitope database thresholds. Multiple sequence alignment was performed to determine the conservation of the epitopes, and different epitopes were docked to their corresponding HLA molecules using AutoDock Vina. The resulting peptide-major histocompatibility complex (pMHC) complexes were then docked to prospect T-cell receptors (TCRs), and the interactions and binding energies of the pMHC and TCR-pMHC model complexes were identified. Our results revealed potential epitopes that may be suitable for vaccine design, including SQSIIAYTM (−7.1 kcal/mol) of HLA-B40:01, VASQSIIAY (−8.2 kcal/mol), and SIIAYTMSL (−7.2 kcal/mol) of HLA-B46:01, IAQYTSALL (−8.0 kcal/mol) of HLA-C01:02, and VASQSIIAY (−8.2 kcal/mol) of HLA-C07:02, as well as SQSIIAYTMSLGAEN, ASQSIIAYTMSLGAE, EMIAQYTSALLAGTI, and NFNGLTGTGVLTESN (HLA-DRB1*09:01). The pMHC complexes formed dominant hydrogen bonds and hydrophobic interactions. TCR-pMHC docking revealed that SQSIIAYTM (−16.0 kcal/mol) has the lowest binding energy and the highest number (128) of binding interactions, primarily consisting of charged-polar and charged-nonpolar interactions. Our findings suggest that epitopes mapping to the furin cleavage site of the SARS-CoV-2 spike protein could be potential targets for vaccine design. Our identified epitopes could serve as a basis for the development of effective vaccines that provide broad coverage across different SARS-CoV-2 variants, particularly in Southeast Asia, where the top two most frequent HLA alleles are prevalent.
Key words: SARS-CoV-2, in silico, vaccine, T-cell epitope, molecular docking
|
