Rxivist logo

SARS-CoV-2 spike (S) mediates entry into cells and is critical for vaccine development against COVID-19. Structural studies have revealed distinct conformations of S, but real-time information that connects these structures, is lacking. Here we apply single-molecule Förster Resonance Energy Transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to hACE2, S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences of convalescent plasma and antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to RBD or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design. ### Competing Interest Statement The authors have declared no competing interest.

Download data

  • Downloaded 1,483 times
  • Download rankings, all-time:
    • Site-wide: 14,642
    • In microbiology: 850
  • Year to date:
    • Site-wide: 28,866
  • Since beginning of last month:
    • Site-wide: 44,085

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide