Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand the human ACE2 receptor on binding affinity and kinetics

Michael I. Barton, Stuart A. MacGowan, Mikhail A. Kutuzov, Omer Dushek, Geoffrey John Barton (Lead / Corresponding author), P. Anton van der Merwe (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

241 Citations (Scopus)
113 Downloads (Pure)

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.

Original languageEnglish
Article numbere70658
Number of pages19
JournaleLife
Volume10
Early online date26 Aug 2021
DOIs
Publication statusPublished - Aug 2021

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

Fingerprint

Dive 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.

Cite this