Genome based evolutionary lineage of SARS-CoV-2 towards the development of novel chimeric vaccine

Abstract

The present study aimed to predict a novel chimeric vaccine 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, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins 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. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data.

Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family

“…The most potent immunogenic proteins were identified for all the viruses after determining the antigenicity score via VaxiJen v2.0 server [ 27 ]. Different physiochemical parameters of the proteins were analyzed through ProtParam tool [ 23 ].

Figure 1 Schematic presentation of the procedures used for the development of cross-reactive vaccine candidate against Arenaviridae family.

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“…OpenBabel v2.3.1 was used to convert the output PDBQT files in PDB format. The docking interaction was visualized with the PyMOL molecular graphics system [ 23 ].…”

“…ProtParam, a tool provided by ExPASy server was used to functionally characterize the vaccine proteins [ 23 ]. Instability and Aliphatic index, isoelectric pH, Molecular weight, GRAVY values, hydropathicity, and estimated half-lives of the vaccine molecules were investigated.…”

“…The most potent immunogenic proteins were identified for all the viruses after determining the antigenicity score via VaxiJen v2.0 server [27]. Different physiochemical parameters of the proteins were analyzed through ProtParam tool [23].…”

“…Therefore, the incorporation of a limited number of additional mutations into the ML29 genome may result in viruses with enhanced virulence [ 21 ]. Though successful in many cases, traditional vaccines such as live-attenuated or inactivated vaccines are associated with several demerits [ 22 , 23 ]. There are evidence of non-virulent organisms getting converted into virulent strains [ 24 , 25 ].…”