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Title | Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. |
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Journal, issue, pages | Science, Vol. 369, Issue 6510, Page 1505-1509, Year 2020 |
Publish date | Sep 18, 2020 |
Authors | Zhe Lv / Yong-Qiang Deng / Qing Ye / Lei Cao / Chun-Yun Sun / Changfa Fan / Weijin Huang / Shihui Sun / Yao Sun / Ling Zhu / Qi Chen / Nan Wang / Jianhui Nie / Zhen Cui / Dandan Zhu / Neil Shaw / Xiao-Feng Li / Qianqian Li / Liangzhi Xie / Youchun Wang / Zihe Rao / Cheng-Feng Qin / Xiangxi Wang / |
PubMed 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 ...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. |
External links | Science / PubMed:32703908 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.49 - 3.9 Å |
Structure data | EMDB-30325, PDB-7cab: EMDB-30326, PDB-7cac: EMDB-30331, PDB-7cah: EMDB-30332, PDB-7cai: EMDB-30333, PDB-7cak: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / Spike glycoprotein / Spike / neutralizing antibodies / neutralizing antibody / SARS-CoV-2 spike glycoprotein |