A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features

The recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viral...

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Autores principales:	Saman Fatihi, Surabhi Rathore, Ankit K. Pathak, Deepanshi Gahlot, Mitali Mukerji, Nidhi Jatana, Lipi Thukral
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	SARS-CoV-2 Spike protein Mutations Lineages Structural features Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a74b1cdf17694d539027508ed9fcaa33
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spelling	oai:doaj.org-article:a74b1cdf17694d539027508ed9fcaa332021-11-20T05:13:33ZA rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features2665-928X10.1016/j.crstbi.2021.11.002https://doaj.org/article/a74b1cdf17694d539027508ed9fcaa332021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2665928X21000258https://doaj.org/toc/2665-928XThe recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viral-host interactions. By temporally tracking 527,988 SARS-CoV-2 genomes, we identified invariant and hypervariable regions within the spike protein. We evaluated combination of mutations from SARS-CoV-2 lineages and found that maximum number of lineage-defining mutations were present in the N-terminal domain (NTD). Based on mutant 3D-structural models of known Variants of Concern (VOCs), we found that structural properties such as accessibility, secondary structural type, and intra-protein interactions at local mutation sites are greatly altered. Further, we observed significant differences between intra-protein networks of wild-type and Delta mutant, with the latter showing dense intra-protein contacts. Extensive molecular dynamics simulations of D614G mutant spike structure with hACE2 further revealed dynamic features with 47.7% of mutations mapping on flexible regions of spike protein. Thus, we propose that significant changes within spike protein structure have occurred that may impact SARS-CoV-2 pathogenesis, and repositioning of vaccine candidates is required to contain the spread of COVID-19 pathogen.Saman FatihiSurabhi RathoreAnkit K. PathakDeepanshi GahlotMitali MukerjiNidhi JatanaLipi ThukralElsevierarticleSARS-CoV-2Spike proteinMutationsLineagesStructural featuresBiology (General)QH301-705.5ENCurrent Research in Structural Biology, Vol 3, Iss , Pp 290-300 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 Spike protein Mutations Lineages Structural features Biology (General) QH301-705.5
spellingShingle	SARS-CoV-2 Spike protein Mutations Lineages Structural features Biology (General) QH301-705.5 Saman Fatihi Surabhi Rathore Ankit K. Pathak Deepanshi Gahlot Mitali Mukerji Nidhi Jatana Lipi Thukral A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
description	The recent release of SARS-CoV-2 genomic data from several countries has provided clues into the potential antigenic drift of the coronavirus population. In particular, the genomic instability observed in the spike protein necessitates immediate action and further exploration in the context of viral-host interactions. By temporally tracking 527,988 SARS-CoV-2 genomes, we identified invariant and hypervariable regions within the spike protein. We evaluated combination of mutations from SARS-CoV-2 lineages and found that maximum number of lineage-defining mutations were present in the N-terminal domain (NTD). Based on mutant 3D-structural models of known Variants of Concern (VOCs), we found that structural properties such as accessibility, secondary structural type, and intra-protein interactions at local mutation sites are greatly altered. Further, we observed significant differences between intra-protein networks of wild-type and Delta mutant, with the latter showing dense intra-protein contacts. Extensive molecular dynamics simulations of D614G mutant spike structure with hACE2 further revealed dynamic features with 47.7% of mutations mapping on flexible regions of spike protein. Thus, we propose that significant changes within spike protein structure have occurred that may impact SARS-CoV-2 pathogenesis, and repositioning of vaccine candidates is required to contain the spread of COVID-19 pathogen.
format	article
author	Saman Fatihi Surabhi Rathore Ankit K. Pathak Deepanshi Gahlot Mitali Mukerji Nidhi Jatana Lipi Thukral
author_facet	Saman Fatihi Surabhi Rathore Ankit K. Pathak Deepanshi Gahlot Mitali Mukerji Nidhi Jatana Lipi Thukral
author_sort	Saman Fatihi
title	A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
title_short	A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
title_full	A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
title_fullStr	A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
title_full_unstemmed	A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features
title_sort	rigorous framework for detecting sars-cov-2 spike protein mutational ensemble from genomic and structural features
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a74b1cdf17694d539027508ed9fcaa33
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A rigorous framework for detecting SARS-CoV-2 spike protein mutational ensemble from genomic and structural features

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