Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants.
Binding Sites
/ genetics
COVID-19
/ epidemiology
COVID-19 Vaccines
/ genetics
Computational Biology
Data Mining
Genetic Variation
Humans
Immunogenetic Phenomena
Models, Molecular
Mutation
Pandemics
/ statistics & numerical data
Protein Domains
Receptors, Virus
SARS-CoV-2
/ genetics
Software
Spike Glycoprotein, Coronavirus
/ genetics
Translational Research, Biomedical
Bioinformatic workflow
COVID mutations
Docker
SARS-CoV-2 genome
SARS-CoV-2 mutation
SARS-CoV-2 vaccine
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
30 12 2020
30 12 2020
Historique:
received:
13
07
2020
accepted:
11
12
2020
entrez:
31
12
2020
pubmed:
1
1
2021
medline:
15
1
2021
Statut:
epublish
Résumé
Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. This work provides a framework able to track down SARS-CoV-2 genomic variability.
Sections du résumé
BACKGROUND
Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity.
METHODS
Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations.
RESULTS
Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs.
CONCLUSIONS
This work provides a framework able to track down SARS-CoV-2 genomic variability.
Identifiants
pubmed: 33380328
doi: 10.1186/s12967-020-02675-4
pii: 10.1186/s12967-020-02675-4
pmc: PMC7772798
doi:
Substances chimiques
COVID-19 Vaccines
0
Receptors, Virus
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
494Subventions
Organisme : Ministero della Salute
ID : Ricerca Corrente 2019
Pays : International
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