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The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice.

Authors
  • Bayarri-Olmos, Rafael1, 2
  • Johnsen, Laust Bruun3
  • Idorn, Manja4
  • Reinert, Line S4
  • Rosbjerg, Anne1, 5
  • Vang, Søren6
  • Hansen, Cecilie Bo2
  • Helgstrand, Charlotte3
  • Bjelke, Jais Rose3
  • Bak-Thomsen, Theresa3
  • Paludan, Søren R4
  • Garred, Peter2
  • Skjoedt, Mikkel-Ole2, 5
  • 1 Recombinant Protein and Antibody Laboratory, Copenhagen University Hospital, Copenhagen, Denmark. , (Denmark)
  • 2 Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. , (Denmark)
  • 3 Novo Nordisk A/S, Måløv, Denmark. , (Denmark)
  • 4 Department of Biomedicine, Aarhus University, Århus, Denmark. , (Denmark)
  • 5 Institute of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 6 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. , (Denmark)
Type
Published Article
Journal
eLife
Publisher
"eLife Sciences Organisation, Ltd."
Publication Date
Nov 25, 2021
Volume
10
Identifiers
DOI: 10.7554/eLife.70002
PMID: 34821555
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant. © 2021, Bayarri-Olmos et al.

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