Cantoni, D. et al. (2022) Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike. EMBO Reports, 23(10), e54322. (doi: 10.15252/embr.202154322) (PMID:35999696) (PMCID:PMC9535765)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Grove, Dr Joe and Robertson, Professor David and Willett, Professor Brian and Bamford, Dr Connor and Cantoni, Dr Diego and Lytras, Spyros |
| Authors: | Cantoni, D., Murray, M. J., Kalemera, M. D., Dicken, S. J., Stejskal, L., Brown, G., Lytras, S., Coey, J. D., McKenna, J., Bridgett, S., Simpson, D., Fairley, D., Thorne, L. G., Reuschl, A.-K., Forrest, C., Ganeshalingham, M., Muir, L., Palor, M., Jarvis, L., Willett, B., Power, U. F., McCoy, L. E., Jolly, C., Towers, G. J., Doores, K. J., Robertson, D. L., Shepherd, A. J., Reeves, M. B., Bamford, C. G.G., and Grove, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | EMBO Reports |
| Publisher: | Wiley |
| ISSN: | 1469-221X |
| ISSN (Online): | 1469-3178 |
| Published Online: | 23 August 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in EMBO Reports 23(10): e54322 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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