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Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

THIS PREPRINT DISCUSSES THE NEW VARIANT, B.1.617, THAT HAS BEEN SPREADING IN INDIA.

Published onApr 21, 2021
Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
key-enterThis Pub is a Preprint of
Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
Description

Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence though natural selection of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. Such mutations are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate minor infectivity deficits associated with other mutations. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain. Comparatively, very little attention has been directed towards spike insertion mutations, which often go unnoticed due to the use of insertion-unaware bioinformatics analysis pipelines. This manuscript describe a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by the independent acquisition of 3-4 additional codons between Arg214 and Asp215 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its progressive increase in frequency and its association with two distinct emerging lineages (A.2.5 and B.1.214.2) warrant further investigation concerning its effects on spike structure and viral infectivity.


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