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Comparative Analysis of SARS-CoV-2 Variants of Concern, Including Omicron, Highlights Their Common and Distinctive Amino Acid Substitution Patterns, Especially at the Spike ORF.

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cam.issuedOnline2022-03-29
dc.contributor.authorNikolaidis, Marios
dc.contributor.authorPapakyriakou, Athanasios
dc.contributor.authorChlichlia, Katerina
dc.contributor.authorMarkoulatos, Panayotis
dc.contributor.authorOliver, Stephen G
dc.contributor.authorAmoutzias, Grigorios D
dc.contributor.orcidPapakyriakou, Athanasios [0000-0003-3931-6232]
dc.contributor.orcidChlichlia, Katerina [0000-0003-4952-0675]
dc.contributor.orcidOliver, Stephen G [0000-0003-3410-6439]
dc.contributor.orcidAmoutzias, Grigorios D [0000-0001-5961-964X]
dc.date.accessioned2022-05-25T01:04:42Z
dc.date.available2022-05-25T01:04:42Z
dc.date.issued2022-03-29
dc.date.updated2022-05-25T01:04:42Z
dc.description.abstractIn order to gain a deeper understanding of the recently emerged and highly divergent Omicron variant of concern (VoC), a study of amino acid substitution (AAS) patterns was performed and compared with those of the other four successful variants of concern (Alpha, Beta, Gamma, Delta) and one closely related variant of interest (VoI-Lambda). The Spike ORF consistently emerges as an AAS hotspot in all six lineages, but in Omicron this enrichment is significantly higher. The progenitors of each of these VoC/VoI lineages underwent positive selection in the Spike ORF. However, once they were established, their Spike ORFs have been undergoing purifying selection, despite the application of global vaccination schemes from 2021 onwards. Our analyses reject the hypothesis that the heavily mutated receptor binding domain (RBD) of the Omicron Spike was introduced via recombination from another closely related Sarbecovirus. Thus, successive point mutations appear as the most parsimonious scenario. Intriguingly, in each of the six lineages, we observed a significant number of AAS wherein the new residue is not present at any homologous site among the other known Sarbecoviruses. Such AAS should be further investigated as potential adaptations to the human host. By studying the phylogenetic distribution of AAS shared between the six lineages, we observed that the Omicron (BA.1) lineage had the highest number (8/10) of recurrent mutations.
dc.identifier.doi10.17863/CAM.84862
dc.identifier.eissn1999-4915
dc.identifier.issn1999-4915
dc.identifier.other35458441
dc.identifier.otherPMC9025783
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337449
dc.languageeng
dc.language.isoeng
dc.publisherMDPI AG
dc.publisher.urlhttp://dx.doi.org/10.3390/v14040707
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101509722
dc.sourceessn: 1999-4915
dc.subjectCOVID-19
dc.subjectOmicron
dc.subjectSARS-CoV-2
dc.subjectamino acid substitutions
dc.subjectdN/dS
dc.subjectevolution
dc.subjectrecurrent mutations
dc.subjectspike
dc.subjectvariants of concern
dc.subjectAmino Acid Substitution
dc.subjectCOVID-19
dc.subjectHumans
dc.subjectPhylogeny
dc.subjectSARS-CoV-2
dc.subjectSpike Glycoprotein, Coronavirus
dc.titleComparative Analysis of SARS-CoV-2 Variants of Concern, Including Omicron, Highlights Their Common and Distinctive Amino Acid Substitution Patterns, Especially at the Spike ORF.
dc.typeArticle
dcterms.dateAccepted2022-03-27
prism.issueIdentifier4
prism.publicationNameViruses
prism.volume14
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/v14040707

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