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Cell Host Microbe
. 2020 Nov 13;S1931-3128(20)30618-1.
doi: 10.1016/j.chom.2020.11.001. Online ahead of print.
Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
Maolin Lu 1 , Pradeep D Uchil 2 , Wenwei Li 2 , Desheng Zheng 2 , Daniel S Terry 3 , Jason Gorman 4 , Wei Shi 4 , Baoshan Zhang 4 , Tongqing Zhou 4 , Shilei Ding 5 , Romain Gasser 5 , J?r?mie Pr?vost 5 , Guillaume Beaudoin-Bussi?res 5 , Sai Priya Anand 6 , Annemarie Laumaea 5 , Jonathan R Grover 2 , Lihong Liu 7 , David D Ho 7 , John R Mascola 4 , Andr?s Finzi 6 , Peter D Kwong 4 , Scott C Blanchard 3 , Walther Mothes 8
Affiliations
- PMID: 33242391
- PMCID: PMC7664471
- DOI: 10.1016/j.chom.2020.11.001
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (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 fluorescence (F?rster) 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 human receptor angiotensin-converting enzyme 2 (hACE2), S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences observed upon exposure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.
Keywords: SARS-CoV-2 spike protein; antibody neutralization; real-time conformational dynamics; receptor ACE2; single-molecule FRET.