Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine

Abstract

SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis.Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level.In addition, disulfide engineering was investigated to accelerate the stability of the protein.Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study.However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.

Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach

“…On this note, multi-epitope vaccine candidates have already been designed against several viruses, including MERS-CoV and SARS-CoV, and their efficacies have been further reported (Almofti et al, 2018;Ul Qamar et al, 2019;Yong et al, 2019). Two related studies have reported the in-silico design of epitope based chimeric vaccine candidates targeting E, M, S and N proteins of SARS-CoV-2, albeit not peer-reviewed (Yazdani et al, 2020;Akhand et al, 2020). Besides, Kibria, Ullah & Miah (2020) performed an immunoinformatic approach to design a 70 aa long multi-epitope vaccine focusing on the the virion outer surface proteins (E, M, and S) (Chan et al, 2020).…”

Spike protein-based epitopes predicted against SARS-CoV-2 through literature mining

“…To determine epitope candidates in the design of the COVID-19 vaccine, researchers all over the world conducted a series of immunoinformatics analysis to predict B- and MHC class I/II T-cell epitopes from the Spike protein, M protein, E protein and N protein of the SARS-CoV-2 virus. We collected 24 published and pre-printed literature [ 14 , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] ] about the SARS-COV-2 epitopes from the outbreak of the epidemic to June 1, 2020 in total ( Supplementary Table 1 ). We discovered that the most frequently used B-cell linear epitope prediction methods were those provided on the Immune Epitope Database (IEDB) server including Bepipred [ 44 ], Kolaskar and Tongaonkar’s antigenic prediction [ 45 ], Emini’s surface accessibility prediction [ 46 ] ( Fig.…”

“…The Spike protein of SARS-COV-2 is regarded as the target due to its formation of characteristic crown of the virus and protruding from the viral envelope [ 15 ]. In order to determine the distribution of epitopes that may be used for vaccine construction, we integrated 24 published articles or preprints [ 14 , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] ] about epitope predictions from January 29, 2020 to June 1, 2020. Based on the results of these researches, we collected all the results about Spike protein for statistical analysis.…”

Computationally Optimized SARS-CoV-2 MHC Class I and II Vaccine Formulations Predicted to Target Human Haplotype Distributions

“…Detailed methods are provided in the online version of this paper and include the following: Baseline vaccine MHC I: (Srivastava et al, 2020) ( Srivastava et al, 2020) Figure 2 Baseline vaccine MHC I: (Herst et al, 2020) ( Herst et al, 2020) Data S1; Table 6 Baseline vaccine MHC I: (Herst et al, 2020)-top16 (Herst et al, 2020) Table 4 Baseline vaccine MHC I: (Baruah and Bose, 2020) ( Baruah and Bose, 2020) Table 1 Baseline vaccine MHC I: (Fast et al, 2020) ( Fast et al, 2020) Table 2 Baseline vaccine MHC I: (Poran et al, 2020) ( Poran et al, 2020) Table S5 Baseline vaccine MHC I: (Vashi et al, 2020) ( Vashi et al, 2020) Table 5 Baseline vaccine MHC I: (Abdelmageed et al, 2020) ( Abdelmageed et al, 2020) Table 2 Baseline vaccine MHC I: (Lee and Koohy, 2020) ( Lee and Koohy, 2020) Table 4 Baseline vaccine MHC I: (Akhand et al, 2020) ( Akhand et al, 2020) Table 2 Baseline vaccine MHC I: (Singh et al, 2020) ( Singh et al, 2020) Table 2 Baseline vaccine MHC I: (Bhattacharya et al, 2020) ( Bhattacharya et al, 2020) Table 2 Baseline vaccine MHC I: (Ahmed et al, 2020) Table 2 Baseline vaccine MHC I: (Saha and Prasad, 2020) ( Saha and Prasad, 2020) Table 1 Baseline vaccine MHC I: (Gupta et al, 2020) ( Gupta et al, 2020) 3 Baseline vaccine MHC II:…”

“…We used EvalVax to evaluate peptide vaccines and megapools proposed by other publications (Lee and Koohy, 2020;Fast et al, 2020;Poran et al, 2020;Bhattacharya et al, 2020;Baruah and Bose, 2020;Abdelmageed et al, 2020;Ahmed et al, 2020;Srivastava et al, 2020;Herst et al, 2020;Vashi et al, 2020;Akhand et al, 2020;Mitra et al, 2020;Khan et al, 2020;Banerjee et al, 2020;Ramaiah and Arumugaswami, 2020;Gupta et al, 2020;Saha and Prasad, 2020;Tahir ul Qamar et al, 2020;Singh et al, 2020;Yarmarkovich et al, 2020;Grifoni et al, 2020a;Nerli and Sgourakis, 2020;Yazdani et al, 2020;Ismail et al, 2020) on metrics including EvalVax-Unlinked and EvalVax-Robust population coverage at different per-individual number of peptide-HLA hits thresholds, expected per-individual number of peptide-HLA hits in White, Black, and Asian populations, percentage of peptides that are predicted to be glycosylated, peptides observed to mutate with a probability greater than 0.001, or peptides that sit on known cleavage sites. We define ''normalized coverage'' as the mean expected per-individual number of peptide-HLA hits for a vaccine divided by the number of peptides in the vaccine.…”