Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain:In silicoanalysis

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we, therefore, designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of nucleocapsid protein that aid in viral replication. Promising antigenic B-cells and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and non-allergenic property. Two CD8<jats:sup>+</jats:sup> and Three CD4<jats:sup>+</jats:sup> T-cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and II alleles. With these selected epitopes, a non-allergenic chimeric peptide vaccine incapable of inducing a Type II hypersensitivity reaction was constructed. The molecular interaction between the toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, <jats:italic>in silico</jats:italic> cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.</jats:p>

Development of a multi-epitope spike glycoprotein vaccine to combat SARS-CoV-2 using the bioinformatics approach

“…3). The only 3D model with more than 70% of its residues in the favored region is deemed a quality structure (Chukwudozie et al, 2020).…”

The Relevance of Bioinformatics Applications in the Discovery of Vaccine Candidates and Potential Drugs for COVID-19 Treatment

“…Chukwudozie et al 6,34 have extensively provided a comprehensive and simplified step in designing peptide vaccines and also provided various approaches in validating them using in silico checkpoints. The steps involved in designing an epitopic peptide vaccine adopting immuno-informatics method include proteomic data retrieval of the protein of interest and adoption of computational immunology analysis of the data, which includes test for antigenicity, allergenicity, peptide toxicity, and epitopic conservancy.…”

“…Other quality checks such as their respective antigenicity, allergenicity, peptide toxicity, and peptide conservancy, which characterize their immunogenicity profile, are considered. A well-summarized and applied process of these steps can be seen in a study conducted by Chukwudozie et al 6,34…”

“…For vaccines, predicting antigenic peptide components, selecting immunogenic carriers amid arrays of immuno-adjuvants that speed up immunogenic response could be achieved using these computational pipelines. 6…”

Induction of Humoral and Cellular Immunity by Intradermal Delivery of SARS-CoV-2 Nucleocapsid Protein Using Dissolvable Microneedles

“…More recently, Chukwudozie et al developed a subcomponent vaccine targeting the SARS-CoV-2 nucleocapsid phosphoprotein RNA binding domain. This vaccine contains both antigenic B cell and T cell epitopes that provide a sufficient antigenic index and nonallergenic property [8]. Importantly, Peng et al revealed that CD8+ T cell responses were associated with milder disease (2-3 weeks recovery rates), whereas more severe cases of SARS-CoV-2 had lower CD8+ T cell responses.…”