Projects per year
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.
FingerprintDive into the research topics of 'Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand the human ACE2 receptor on binding affinity and kinetics'. Together they form a unique fingerprint.
1/09/18 → 31/08/23
Extending The Jalview Resource for Biological Sequence Alignment and Analysis (Biomedical Resource application)
1/09/14 → 28/02/21
1/03/13 → 31/08/18
- 1 Preprint
Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kineticsBarton, M. I., MacGowan, S., Kutuzov, M., Dushek, O., Barton, G. J. & Merwe, P. A. V. D., 24 May 2021, BioRxiv, 39 p.
Research output: Working paper/Preprint › PreprintFile10 Downloads (Pure)