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Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA v...

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Autores principales: Gerdol, Marco, Dishnica, Klevia, Giorgetti, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743576/
https://www.ncbi.nlm.nih.gov/pubmed/35021068
http://dx.doi.org/10.1016/j.virusres.2022.198674
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author Gerdol, Marco
Dishnica, Klevia
Giorgetti, Alejandro
author_facet Gerdol, Marco
Dishnica, Klevia
Giorgetti, Alejandro
author_sort Gerdol, Marco
collection PubMed
description Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence, though natural selection, of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. These are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate infectivity deficits associated with other non-synonymous substitutions. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain (NTD). Comparatively, very little attention had been directed towards spike insertion mutations prior to the emergence of the B.1.1.529 (omicron) lineage. This manuscript describes a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by at least 49 independent acquisitions of 1–8 additional codons between Val213 and Leu216 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its association with two distinct formerly widespread lineages (A.2.5 and B.1.214.2), with the quickly spreading omicron and with other VOCs and VOIs warrants further investigation concerning its effects on spike structure and viral infectivity.
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spelling pubmed-87435762022-01-10 Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein Gerdol, Marco Dishnica, Klevia Giorgetti, Alejandro Virus Res Article Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence, though natural selection, of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. These are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate infectivity deficits associated with other non-synonymous substitutions. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain (NTD). Comparatively, very little attention had been directed towards spike insertion mutations prior to the emergence of the B.1.1.529 (omicron) lineage. This manuscript describes a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by at least 49 independent acquisitions of 1–8 additional codons between Val213 and Leu216 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its association with two distinct formerly widespread lineages (A.2.5 and B.1.214.2), with the quickly spreading omicron and with other VOCs and VOIs warrants further investigation concerning its effects on spike structure and viral infectivity. Elsevier B.V. 2022-03 2022-01-10 /pmc/articles/PMC8743576/ /pubmed/35021068 http://dx.doi.org/10.1016/j.virusres.2022.198674 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Gerdol, Marco
Dishnica, Klevia
Giorgetti, Alejandro
Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title_full Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title_fullStr Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title_full_unstemmed Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title_short Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
title_sort emergence of a recurrent insertion in the n-terminal domain of the sars-cov-2 spike glycoprotein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743576/
https://www.ncbi.nlm.nih.gov/pubmed/35021068
http://dx.doi.org/10.1016/j.virusres.2022.198674
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