pubmed.ncbi.nlm.nih.gov

Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile - PubMed

  • ️Sat Jan 01 2022

Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile

Mohammad Alkhatib et al. Microbiol Spectr. 2022.

Abstract

The process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversification is still ongoing and has very recently led to the emergence of a new variant of concern (VOC), defined as Omicron or B.1.1.529. Omicron VOC is the most divergent variant identified so far and has generated immediate concern for its potential capability to increase SARS-CoV-2 transmissibility and, more worryingly, to escape therapeutic and vaccine-induced antibodies. Nevertheless, a clear definition of the Omicron VOC mutational spectrum is still missing. Herein, we provide a comprehensive definition and functional characterization (in terms of infectivity and/or antigenicity) of mutations characterizing the Omicron VOC. In particular, 887,475 SARS-CoV-2 Omicron VOC whole-genome sequences were retrieved from the GISAID database and used to precisely define its specific patterns of mutations across the different viral proteins. In addition, the functional characterization of Omicron VOC spike mutations was finely discussed according to published manuscripts. Lastly, residues characterizing the Omicron VOC and the previous four VOCs (Alpha, Beta, Gamma, and Delta) were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, our study will assist with deciphering the Omicron VOC mutational profile and will shed more light on its clinical implications. This is critical considering that Omicron VOC is currently the predominant variant worldwide. IMPORTANCE The Omicron variant of concern (VOC) has a peculiar spectrum of mutations characterized by the acquisition of mutations or deletions rarely detected in previously identified variants, particularly in the spike glycoprotein. Such mutations, mostly residing in the receptor-binding domain, could play a pivotal role in enhancing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity (by increasing binding affinity for ACE2), jeopardizing spike recognition by therapeutic and vaccine-induced antibodies and causing diagnostic assay failure. To our knowledge, this is one of the first exhaustive descriptions of newly emerged mutations underlying the Omicron VOC and its biological and clinical implications.

Keywords: B.1.1.519; COVID-19; SARS-CoV-2; emerging variants; mutations; omicron; pandemic; variant of concern.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIG 1
FIG 1

(a) Schematic illustration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and its variants of concern along with their relevant mutations that characterize each protein of interest. Mutations were defined as amino acid substitutions/deletions/insertions that occurred in 75% of sequences using the NC_045512.2 as the reference sequence. Residues in red are those that directly interact with ACE2. Mutations in bold black refer to the shared mutations by at least two variants of concern, while those in bold blue refer to the unique Omicron mutations. *Mutations at residues 417, 440, and 446 in the receptor-binding domain (RBD) spike represent original Omicron consensus according to earlier prevalence of greater than 75%, while currently, the new prevalence values are 51.3, 53.9, and 54,9%, respectively. (b) Spike mutations underlying the currently circulating Omicron sublineages BA.1, BA.1.1, BA.2, and BA.3. Blue color refers to those mutations shared by the four sublineages.

FIG 2
FIG 2

Three-dimensional representation of SARS-CoV-2 spike protein reporting residues characterizing the five variants of concern (VOCs). The protein is shown as a gray cartoon. The Alpha B.1.1.7, Beta B.1.351, Gamma P.1, Delta B.1.617.2 + AY.X, and Omicron B.1.1.529 VOCs are represented as magenta, yellow, cyan, forest green, and blue spheres, respectively. The shared mutated residues present in at least two VOCs are reported as red spheres.

Similar articles

Cited by

References

    1. World Health Organization. 2021. Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.....
    1. European Centre for Disease Prevention and Control. 2021. Threat assessment brief: implications of the emergence and spread of the SARS-CoV-2 B.1.1. 529 variant of concern (Omicron) for the EU/EEA. https://www.ecdc.europa.eu/en/publications-data/threat-assessment-brief-....
    1. Centers for Disease Control and Prevention. 2021. Science brief: Omicron (B.1.1.529) variant. https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/scienti.... - PubMed
    1. Kupferschmidt KAI. 2021. Where did “weird” Omicron come from? Science 374:1179–1179. doi:10.1126/science.acx9738. - DOI - PubMed
    1. Venkatakrishnan A, Praveen A, Patrick L, Rohit S, Bharathwaj R, Michiel JN, Venky S. 2021. Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin. OSF Preprints. 10.31219/osf.io/f7txy. - DOI

Publication types

MeSH terms

Substances

Supplementary concepts