Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand the human ACE2 receptor on binding affinity and kinetics
- University of Oxford, United Kingdom
- University of Dundee, United Kingdom
Abstract
The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations, and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351) and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.
Data availability
All data generated and analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Geoffrey John Barton
P Anton van der Merwe
Funding
Wellcome Trust (207537/Z/17/Z828)
- Mikhail A Kutuzov
- Omer Dushek
Biotechnology and Biological Sciences Research Council (BB/J019364/1)
- Stuart A MacGowan
- Geoffrey John Barton
Biotechnology and Biological Sciences Research Council (BB/R014752/1)
- Stuart A MacGowan
- Geoffrey John Barton
Wellcome Trust (101651/Z/13/Z).)
- Stuart A MacGowan
- Geoffrey John Barton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Barton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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