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On the Origins of Omicron's Unique Spike Gene Insertion.
Venkatakrishnan, A J; Anand, Praveen; Lenehan, Patrick J; Suratekar, Rohit; Raghunathan, Bharathwaj; Niesen, Michiel J M; Soundararajan, Venky.
  • Venkatakrishnan AJ; nference, Cambridge, MA 02139, USA.
  • Anand P; nference Labs, Bengaluru 560017, Karnataka, India.
  • Lenehan PJ; nference, Cambridge, MA 02139, USA.
  • Suratekar R; nference Labs, Bengaluru 560017, Karnataka, India.
  • Raghunathan B; nference, Toronto, ON M5V 1M1, Canada.
  • Niesen MJM; nference, Cambridge, MA 02139, USA.
  • Soundararajan V; nference, Cambridge, MA 02139, USA.
Vaccines (Basel) ; 10(9)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2033181
ABSTRACT
The emergence of a heavily mutated SARS-CoV-2 variant (Omicron; Pango lineage B.1.1.529 and BA sublineages) and its rapid spread to over 75 countries raised a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its clinical phenotypes which are shared with or distinctive from those of other SARS-CoV-2 variants. We compared the mutations of the initially circulating Omicron variant (now known as BA.1) with prior variants of concern (Alpha, Beta, Gamma, and Delta), variants of interest (Lambda, Mu, Eta, Iota, and Kappa), and ~1500 SARS-CoV-2 lineages constituting ~5.8 million SARS-CoV-2 genomes. Omicron's Spike protein harbors 26 amino acid mutations (23 substitutions, 2 deletions, and 1 insertion) that are distinct compared to other variants of concern. While the substitution and deletion mutations appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) was not previously observed in any other SARS-CoV-2 lineage. Here, we consider and discuss various mechanisms through which the nucleotide sequence encoding for ins214EPE could have been acquired, including local duplication, polymerase slippage, and template switching. Although we are not able to definitively determine the mechanism, we highlight the plausibility of template switching. Analysis of the homology of the inserted nucleotide sequence and flanking regions suggests that this template-switching event could have involved the genomes of SARS-CoV-2 variants (e.g., the B.1.1 strain), other human coronaviruses that infect the same host cells as SARS-CoV-2 (e.g., HCoV-OC43 or HCoV-229E), or a human transcript expressed in a host cell that was infected by the Omicron precursor.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines10091509

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines10091509