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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Host+Microbe 2020 ; 28 (6): 880-891.e8 Nephropedia Template TP
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Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles #MMPMID33242391
Lu M; Uchil PD; Li W; Zheng D; Terry DS; Gorman J; Shi W; Zhang B; Zhou T; Ding S; Gasser R; Prevost J; Beaudoin-Bussieres G; Anand SP; Laumaea A; Grover JR; Liu L; Ho DD; Mascola JR; Finzi A; Kwong PD; Blanchard SC; Mothes W
Cell Host Microbe 2020[Dec]; 28 (6): 880-891.e8 PMID33242391show ga
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 (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 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.