TY - JOUR
AU - Barton, Michael Ian
AU - MacGowan, Stuart A.
AU - Kutuzov, Mikhail
AU - Dushek, Omer
AU - Barton, Geoffrey J.
AU - van der Merwe, P. Anton
PY - 2021
DA - May
TI - Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics
JO - eLife
VL - 10
DO - https://doi.org/10.1101/2021.05.18.444646
AB - 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 domain are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the more transmissible B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD domain 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 variants first identified in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P1). 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 primarily enhance transmission, the K417N/T mutations facilitate immune escape, and the E484K mutation facilitates both transmission and immune escape.
PB - eLife Sciences Publications
UR - https://discovery.dundee.ac.uk/en/publications/99621735-a681-4b09-acfe-a45a8962cabd
KW - Coronavirus (COVID-19)
ER