TY - JOUR TI - Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike AU - Díaz-Salinas, Marco A AU - Li, Qi AU - Ejemel, Monir AU - Yurkovetskiy, Leonid AU - Luban, Jeremy AU - Shen, Kuang AU - Wang, Yang AU - Munro, James B A2 - Gonzalez, Ruben L A2 - Aldrich, Richard W A2 - Bowen, Mark E VL - 11 PY - 2022 DA - 2022/03/24 SP - e75433 C1 - eLife 2022;11:e75433 DO - 10.7554/eLife.75433 UR - https://doi.org/10.7554/eLife.75433 AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Förster resonance energy transfer (smFRET) imaging, we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and in the presence of the D614G mutation. We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails. KW - virus entry KW - protein dynamics KW - single-molecule biophysics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -