Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis

Abstract

The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2). A computational approach was adopted to identify multiepitope vaccine candidates against SARS-CoV-2 based on S, N and M proteins being able to elicit both humoral and cellular immune responses. In this study, the sequence of the virus was obtained from NCBI database and analyzed with in silico tools such as NetMHCpan, IEDB, BepiPred, NetCTL, Tap transport/proteasomal cleavage, Pa 3 P, GalexyPepDock, I-TASSER, Ellipro and ClusPro. To identify the most immunodominant regions, after analysis of population coverage and epitope conservancy, we proposed three different constructs based on linear B-cell, CTL and HTL epitopes. The 3D structure of constructs was assessed to find discontinuous B-cell epitopes. Among CTL predicted epitopes, S 257-265 , S 603-611 and S 360-368 , and among HTL predicted epitopes, N 167-181 , S 313-330 and S 1110-1126 had better MHC binding rank. We found one putative CTL epitope, S 360-368 related to receptor-binding domain (RBD) region for S protein. The predicted epitopes were non-allergen and showed a high quality of proteasomal cleavage and Tap transport efficiency and 100% conservancy within four different clades of SARS-CoV-2. For CTL and HTL epitopes, the highest population coverage of the world’s population was calculated for S 27-37 with 86.27% and for S 196-231 , S 303-323 , S 313-330 , S 1009-1030 and N 328-349 with 90.33%, respectively. We identified overall 10 discontinuous B-cell epitopes for three multiepitope constructs. All three constructs showed strong interactions with TLRs 2, 3 and 4 supporting the hypothesis of SARS-CoV-2 susceptibility to TLRs 2, 3 and 4 like other Coronaviridae families. These data demonstrated that the novel designed multiepitope constructs can contribute to develop SARS-CoV-2 peptide vaccine candidates. The in vivo studies are underway using several vaccination strategies.

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

“…It is important to take into account AMP development programs that are used to predict a possible immune response and allergic reactions to a specific peptide structure [ 238 ]. This validation is especially important for drug development based on AMPs, in particular, antiviral drugs, which will be discussed in more detail in the final section of this review.…”

“…High-performance in silico technologies currently allows the development of new approaches to the creation of peptide vaccines. Antigenic epitopes found in viral proteins can simultaneously meet several criteria, including immunodominant regions, non-allergenicity, population coverage, and lack of variability (conservatism) for efficient binding and molecular interaction with HLA (human leukocyte antigen) and TLR (toll-like receptor) alleles [ 238 ]. To evaluate the effectiveness of peptide vaccines against SARS-CoV-2, the frequencies of the HLA haplotypes can be used to predict the coverage of the developed vaccine.…”

Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study

“…In studies conducted by Kar et al [ 78 ], Dar et al [ 79 ], and Kumar et al [ 80 ], S protein alone was used as a target for epitope prediction. However, in other pieces of research conducted by Kalita et al [ 81 ] and Khairkhah et al [ 82 ], S, M, and N protein were identified as target antigens. Furthermore, S, E, and N proteins were reported as target antigens by Kumar et al [ 83 ] .…”

Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein

“…According to the prediction of the transmembrane helix topology in a three-dimensional (3-D) model [ 22 ], the N- and C-terminal portions of the membrane glycoprotein were exposed outside and inside the particle of SARS-CoV-2, respectively. Both B-cell and T-cell epitopes within a highly conserved region of membrane protein have been revealed [ 23 , 24 ]. Results from a recent study demonstrated that membrane glycoprotein inhibited the type I and III interferon production by targeting the signaling mediated by retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) [ 25 ].…”