Real-time conformational dynamics of SARS-CoV-2 spikes on virus particles
Maolin Lu; Pradeep D. Uchil; Wenwei Li; Desheng Zheng; Jason Gorman; Wei Shi; Baoshan Zhang; Tongqing Zhou; Shilei Ding; Romain Gasser; Jeremie Prevost; Guillaume Beaudoin-Bussieres; Sai Priya Anand; Annemarie Laumaea; Jonathan R. Grover; Liu Lihong; David D Ho; John Mascola; Andres Finzi; Peter D. Kwong; Walther Mothes.
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| PREPRINT-BIORXIV | ID: ppbiorxiv-286948
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 Forster 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.
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