TY - JOUR
AU - Cantoni, Diego
AU - Murray, Matthew J.
AU - Kalemera, Mphatso D.
AU - Dicken, Samuel J.
AU - Stejskal, Lenka
AU - Brown, Georgina
AU - Lytras, Spyros
AU - Coey, Jonathon D.
AU - McKenna, James P.
AU - Bridgett, Stephen
AU - Simpson, David
AU - Fairley, Derek J.
AU - Thorne, Lucy G.
AU - Reuschl, Ann-Kathrin
AU - Forrest, Calum
AU - Ganeshalingham, Maaroothen
AU - Muir, Luke
AU - Palor, Machaela
AU - Jarvis, Lisa
AU - Willett, Brian
AU - Power, Ultan F.
AU - McCoy, Laura E.
AU - Jolly, Clare
AU - Towers, Greg J.
AU - Doores, Katie J.
AU - Robertson, David L.
AU - Shepherd, Adrian J.
AU - Reeves, Matthew B.
AU - Bamford, Connor G.G.
AU - Grove, Joe
PY - 2022
DA - August
TI - Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike
JO - EMBO Reports
DO - https://doi.org/10.15252/embr.202154322
AB - 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.
PB - Wiley
UR - http://eprints.gla.ac.uk/277406/
KW - Coronavirus (COVID-19)
ER