Revealing the effect of SARS-CoV-2 spike stabilisation on receptor binding dynamics with single molecule mass photometry

Here we show using mass photometry how proline substitutions, commonly used for SARS-CoV-2 spike stabilisation and vaccine design, directly impedes ACE2 receptor interactions via dynamics of open and closed states. Conformational changes and ACE2 binding were influenced by spike variant and temperature, but independent of site-specific N-glycosylation.