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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Rafael Bayarri-Olmos, Københavns Universitet
  • ,
  • Laust Bruun Johnsen, Novo Nordisk AS
  • ,
  • Manja Idorn
  • Line S. Reinert
  • Anne Rosbjerg, Københavns Universitet
  • ,
  • Søren Vang
  • Cecilie Bo Hansen, Københavns Universitet
  • ,
  • Charlotte Helgstrand, Novo Nordisk AS
  • ,
  • Jais Rose Bjelke, Novo Nordisk AS
  • ,
  • Theresa Bak-Thomsen, Novo Nordisk AS
  • ,
  • Søren R. Paludan
  • Peter Garred, Københavns Universitet
  • ,
  • Mikkel Ole Skjoedt, Københavns Universitet

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 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 eight-fold affinity increase towards human ACE-2. In accordance with this, transgenic hACE-2 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.

OriginalsprogEngelsk
Artikelnummere70002
TidsskrifteLife
Vol/bind10
ISSN2050-084X
DOI
StatusUdgivet - nov. 2021

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