TY - JOUR TI - Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics AU - Barton, Michael I AU - MacGowan, Stuart A AU - Kutuzov, Mikhail A AU - Dushek, Omer AU - Barton, Geoffrey John AU - van der Merwe, P Anton A2 - Fouchier, Ron AM A2 - Van der Meer, Jos W A2 - Fouchier, Ron AM VL - 10 PY - 2021 DA - 2021/08/26 SP - e70658 C1 - eLife 2021;10:e70658 DO - 10.7554/eLife.70658 UR - https://doi.org/10.7554/eLife.70658 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 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. KW - COVID-19 KW - SARS-CoV-2 KW - ACE2 KW - viral receptor KW - affinity KW - coronavirus JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -