4.6 Article

Bioinformatics prediction of B and T cell epitopes within the spike and nucleocapsid proteins of SARS-CoV2

Journal

JOURNAL OF INFECTION AND PUBLIC HEALTH
Volume 14, Issue 2, Pages 169-178

Publisher

ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.jiph.2020.12.006

Keywords

SARS CoV2; Furin cleavage site; Genetic distance; NH2 Terminal Domain; Phylogenetic tree

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This study focuses on identifying immunogenic targets for better vaccine development and immunotherapy of SARS CoV2 infection. The research revealed a deletion of key amino acid residues in the S protein, affecting the structure and function of the protein. A set of B and T cell epitopes were proposed based on immune response data for post-infection immunity.
Background: The striking difference in severity of SARS CoV2 infection among global population is partly attributed to viral factors. With the spike (S) and nucleocapsid (N) are the most immunogenic subunits, genetic diversity and antigenicity of S and N are key players in virulence and in vaccine development. Aim: This paper aims at identifying immunogenic targets for better vaccine development and/or immunotherapy of COVID 19 pandemic. Methods: 18 complete genomes of SARS CoV2 (n = 14), SARS CoV (n= 2) and MERS CoV (n = 2) were examined. Bioinformatics of viral genetics and protein folding allowed functional tuning of NH2 Terminal Domain (NTD) of S protein and development of epitope maps for B and T cell responses. Conclusion: A deletion of amino acid residues Y144 and G107 were discovered in NTD of S protein derived from Indian and French isolates resulting in altered pocket structure exclusively located in NTD and reduced affinity of NTD binding to endogenous nAbs and disrupted NTD mediated cell entry. We therefore, proposed a set of B and T cell epitopes based on Immune Epitope Database, homologous epitopes for nAbs in convalescent plasma post SARS CoV infection and functional domains of S (NTD, Receptor Binding domain and the unique polybasic Furin cleavage site at S1/S2 junction). Nevertheless, laboratory data are required to develop vaccine and immunotherapeutics. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences.

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