EMD-30325

Single-particle
3.52 Å
EMD-30325 Deposition: 08/06/2020
Map released: 16/12/2020
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-30325

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

EMD-30325

Single-particle
3.52 Å
EMD-30325 Deposition: 08/06/2020
Map released: 16/12/2020
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 spike glycoprotein trimer
Fitted models: 7cab (Avg. Q-score: 0.476)

Deposition Authors: Zhe L, Cao L
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.
Lv Z , Deng YQ , Ye Q , Cao L , Sun CY , Fan C , Huang W , Sun S , Sun Y , Zhu L , Chen Q , Wang N , Nie J, Cui Z , Zhu D , Shaw N , Li XF , Li Q, Xie L , Wang Y , Rao Z , Qin CF , Wang X
(2020) Science , 369 , 1505 - 1509
PUBMED: 32703908
DOI: doi:10.1126/science.abc5881
ISSN: 1095-9203
ASTM: SCIEAS
Abstract:
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.