Mass photometry reveals SARS-CoV-2 spike stabilisation to impede ACE2 binding through altered conformational dynamics.

Here we show using mass photometry how proline substitutions, commonly used for SARS-CoV-2 spike stabilisation in vaccine design, directly affects 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.