Cantoni, Diego;
Murray, Matthew;
Kalemera, Mphatso;
Dicken, Samuel;
Stejskal, Lenka;
Brown, Georgina;
Lytros, Spyros;
... Grove, Joe; + view all
(2022)
Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike.
EMBO Reports
, Article e54322. 10.15252/embr.202154322.
(In press).
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Abstract
The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N-terminal domain (NTD) of spike; the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine-tune spike; this may provide a mechanism for SARS-CoV-2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune-driven antigenic variation and ongoing adaptation to a new host.
| Type: | Article |
|---|---|
| Title: | Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/embr.202154322 |
| Publisher version: | https://doi.org/10.15252/embr.202154322 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10154141 |
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