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
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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. / Bayarri-Olmos, Rafael; Johnsen, Laust Bruun; Idorn, Manja; Reinert, Line S.; Rosbjerg, Anne; Vang, Søren; Hansen, Cecilie Bo; Helgstrand, Charlotte; Bjelke, Jais Rose; Bak-Thomsen, Theresa; Paludan, Søren R.; Garred, Peter; Skjoedt, Mikkel-Ole.
I: eLife, Bind 10, e70002, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - 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
AU - Bayarri-Olmos, Rafael
AU - Johnsen, Laust Bruun
AU - Idorn, Manja
AU - Reinert, Line S.
AU - Rosbjerg, Anne
AU - Vang, Søren
AU - Hansen, Cecilie Bo
AU - Helgstrand, Charlotte
AU - Bjelke, Jais Rose
AU - Bak-Thomsen, Theresa
AU - Paludan, Søren R.
AU - Garred, Peter
AU - Skjoedt, Mikkel-Ole
N1 - Publisher Copyright: © 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.7554/eLife.70002
DO - 10.7554/eLife.70002
M3 - Journal article
C2 - 34821555
AN - SCOPUS:85120159055
VL - 10
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e70002
ER -
ID: 301451848