Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential

Global efforts are being made to monitor the evolution of SARS-CoV-2, aiming for early identification of genotypes providing increased infectivity or virulence. However, viral lineage-focused tracking might fail in early detection of advantageous mutations emerging independently across phylogenies....

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Autores principales:	Slawomir Kubik, Nils Arrigo, Jaume Bonet, Zhenyu Xu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 genome coronavirus spike NTD W152 viral evolution neutralizing antibody Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cc58a2f8810241f7acdaa11bf478c6e7
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spelling	oai:doaj.org-article:cc58a2f8810241f7acdaa11bf478c6e72021-11-25T19:12:22ZMutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential10.3390/v131121141999-4915https://doaj.org/article/cc58a2f8810241f7acdaa11bf478c6e72021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2114https://doaj.org/toc/1999-4915Global efforts are being made to monitor the evolution of SARS-CoV-2, aiming for early identification of genotypes providing increased infectivity or virulence. However, viral lineage-focused tracking might fail in early detection of advantageous mutations emerging independently across phylogenies. Here, the emergence patterns of Spike mutations were investigated in sequences deposited in local and global databases to identify mutational hotspots across phylogenies and we evaluated their impact on SARS-CoV-2 evolution. We found a striking increase in the frequency of recruitment of diverse substitutions at a critical residue (W152), positioned in the N-terminal domain (NTD) of the Spike protein, observed repeatedly across independent phylogenetic and geographical contexts. These mutations might have an impact on the evasion of neutralizing antibodies. Finally, we found that NTD is a region exhibiting particularly high frequency of mutation recruitments, suggesting an evolutionary path in which the virus maintains optimal efficiency of ACE2 binding combined with the flexibility facilitating the immune escape. We conclude that adaptive mutations, frequently present outside of the receptor-binding domain, can emerge in virtually any SARS-CoV-2 lineage and at any geographical location. Therefore, surveillance should not be restricted to monitoring defined lineages alone.Slawomir KubikNils ArrigoJaume BonetZhenyu XuMDPI AGarticleSARS-CoV-2 genomecoronavirusspike NTDW152viral evolutionneutralizing antibodyMicrobiologyQR1-502ENViruses, Vol 13, Iss 2114, p 2114 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 genome coronavirus spike NTD W152 viral evolution neutralizing antibody Microbiology QR1-502
spellingShingle	SARS-CoV-2 genome coronavirus spike NTD W152 viral evolution neutralizing antibody Microbiology QR1-502 Slawomir Kubik Nils Arrigo Jaume Bonet Zhenyu Xu Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
description	Global efforts are being made to monitor the evolution of SARS-CoV-2, aiming for early identification of genotypes providing increased infectivity or virulence. However, viral lineage-focused tracking might fail in early detection of advantageous mutations emerging independently across phylogenies. Here, the emergence patterns of Spike mutations were investigated in sequences deposited in local and global databases to identify mutational hotspots across phylogenies and we evaluated their impact on SARS-CoV-2 evolution. We found a striking increase in the frequency of recruitment of diverse substitutions at a critical residue (W152), positioned in the N-terminal domain (NTD) of the Spike protein, observed repeatedly across independent phylogenetic and geographical contexts. These mutations might have an impact on the evasion of neutralizing antibodies. Finally, we found that NTD is a region exhibiting particularly high frequency of mutation recruitments, suggesting an evolutionary path in which the virus maintains optimal efficiency of ACE2 binding combined with the flexibility facilitating the immune escape. We conclude that adaptive mutations, frequently present outside of the receptor-binding domain, can emerge in virtually any SARS-CoV-2 lineage and at any geographical location. Therefore, surveillance should not be restricted to monitoring defined lineages alone.
format	article
author	Slawomir Kubik Nils Arrigo Jaume Bonet Zhenyu Xu
author_facet	Slawomir Kubik Nils Arrigo Jaume Bonet Zhenyu Xu
author_sort	Slawomir Kubik
title	Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
title_short	Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
title_full	Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
title_fullStr	Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
title_full_unstemmed	Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential
title_sort	mutational hotspot in the sars-cov-2 spike protein n-terminal domain conferring immune escape potential
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cc58a2f8810241f7acdaa11bf478c6e7
work_keys_str_mv	AT slawomirkubik mutationalhotspotinthesarscov2spikeproteinnterminaldomainconferringimmuneescapepotential AT nilsarrigo mutationalhotspotinthesarscov2spikeproteinnterminaldomainconferringimmuneescapepotential AT jaumebonet mutationalhotspotinthesarscov2spikeproteinnterminaldomainconferringimmuneescapepotential AT zhenyuxu mutationalhotspotinthesarscov2spikeproteinnterminaldomainconferringimmuneescapepotential
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Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential

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