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Experimental evidence for enhanced receptor binding by rapidly spreading SARS-CoV-2 variants

Charlie Laffeber, Kelly de Koning, Roland Kanaar, Joyce HG Lebbink
doi: https://doi.org/10.1101/2021.02.22.432357
Charlie Laffeber
1Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
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Kelly de Koning
1Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
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Roland Kanaar
1Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
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Joyce HG Lebbink
1Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
2Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
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  • For correspondence: j.lebbink@erasmusmc.nl
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Abstract

Rapidly spreading new variants of SARS-CoV-2 carry multiple mutations in the viral spike protein which attaches to the angiotensin converting enzyme 2 (ACE2) receptor on host cells. Among these mutations are amino acid changes N501Y (lineage B.1.1.7, first identified in the UK), and the combination N501Y, E484K, K417N (B.1.351, first identified in South Africa), all located at the interface on the receptor binding domain (RBD). We experimentally establish that RBD containing the N501Y mutation results in 9-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation does not significantly influence the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 3-fold weaker than N501Y. The recently emerging double mutant E484K/N501Y binds as tight as N501Y. The independent evolution of lineages containing mutations with different effects on receptor binding affinity, viral transmission and immune evasion underscores the importance of global viral genome surveillance and functional characterization.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 22, 2021.
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Experimental evidence for enhanced receptor binding by rapidly spreading SARS-CoV-2 variants
Charlie Laffeber, Kelly de Koning, Roland Kanaar, Joyce HG Lebbink
bioRxiv 2021.02.22.432357; doi: https://doi.org/10.1101/2021.02.22.432357
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Experimental evidence for enhanced receptor binding by rapidly spreading SARS-CoV-2 variants
Charlie Laffeber, Kelly de Koning, Roland Kanaar, Joyce HG Lebbink
bioRxiv 2021.02.22.432357; doi: https://doi.org/10.1101/2021.02.22.432357

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