TY - JOUR TI - 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 A2 - Sato, Kei A2 - Davenport, Miles P VL - 10 PY - 2021 DA - 2021/11/25 SP - e70002 C1 - eLife 2021;10:e70002 DO - 10.7554/eLife.70002 UR - https://doi.org/10.7554/eLife.70002 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 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. KW - immunology KW - epidemiology KW - SARS-CoV-2 KW - mouse model KW - human JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -