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

eLife

Geoffrey John Barton¹  Stuart A MacGowan¹  Mikhail A Kutuzov²  Omer Dushek²  Michael I Barton²  P Anton van der Merwe² 

[1] School of Life Sciences, University of Dundee, Dundee, United Kingdom;Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom;

关键词: COVID-19;    SARS-CoV-2;    ACE2;    viral receptor;    affinity;    coronavirus;    Human;   

DOI  :  10.7554/eLife.70658

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY