tetano
Editor, Senior Moderator
Microbiol Spectr
. 2022 Mar 30;e0273221.
doi: 10.1128/spectrum.02732-21. Online ahead of print.
Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile
Mohammad Alkhatib[SUP] 1 [/SUP], Romina Salpini[SUP] 1 [/SUP], Luca Carioti[SUP] 1 [/SUP], Francesca Alessandra Ambrosio[SUP] 2 [/SUP], Stefano D'Anna[SUP] 1 [/SUP], Leonardo Duca[SUP] 1 [/SUP], Giosuè Costa[SUP] 2 3 [/SUP], Maria Concetta Bellocchi[SUP] 1 [/SUP], Lorenzo Piermatteo[SUP] 1 [/SUP], Anna Artese[SUP] 2 3 [/SUP], Maria Mercedes Santoro[SUP] 1 [/SUP], Stefano Alcaro[SUP] 2 3 [/SUP], Valentina Svicher[SUP] #[/SUP][SUP] 4 [/SUP], Francesca Ceccherini-Silberstein[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
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.
. 2022 Mar 30;e0273221.
doi: 10.1128/spectrum.02732-21. Online ahead of print.
Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile
Mohammad Alkhatib[SUP] 1 [/SUP], Romina Salpini[SUP] 1 [/SUP], Luca Carioti[SUP] 1 [/SUP], Francesca Alessandra Ambrosio[SUP] 2 [/SUP], Stefano D'Anna[SUP] 1 [/SUP], Leonardo Duca[SUP] 1 [/SUP], Giosuè Costa[SUP] 2 3 [/SUP], Maria Concetta Bellocchi[SUP] 1 [/SUP], Lorenzo Piermatteo[SUP] 1 [/SUP], Anna Artese[SUP] 2 3 [/SUP], Maria Mercedes Santoro[SUP] 1 [/SUP], Stefano Alcaro[SUP] 2 3 [/SUP], Valentina Svicher[SUP] #[/SUP][SUP] 4 [/SUP], Francesca Ceccherini-Silberstein[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
- PMID: 35352942
- DOI: 10.1128/spectrum.02732-21
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.