EMD-12282

Single-particle
4.6 Å
EMD-12282 Deposition: 30/01/2021
Map released: 03/03/2021
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-12282

EM structure of SARS-CoV-2 Spike glycoprotein in complex with COVOX-253H165L Fab

EMD-12282

Single-particle
4.6 Å
EMD-12282 Deposition: 30/01/2021
Map released: 03/03/2021
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Severe acute respiratory syndrome coronavirus 2
Sample: Complex of SARS-COV-2 spike glycoprotein with COVOX-253H165L Fab
Fitted models: 7ndb (Avg. Q-score: 0.197)

Deposition Authors: Duyvesteyn HME , Zhao Y , Ren J , Stuart D
The antigenic anatomy of SARS-CoV-2 receptor binding domain.
PUBMED: 33756110
DOI: doi:10.1016/j.cell.2021.02.032
ISSN: 1097-4172
Abstract:
Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.