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

doi:10.1126/science.abc5881

GSTDTAP > 气候变化

DOI	10.1126/science.abc5881
	Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
	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
	2020-09-18
发表期刊	Science
出版年	2020
英文摘要	In response to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immune system makes antibodies, many of which target the spike protein, a key player in host cell entry. Antibodies that potently neutralize the virus hold promise as therapeutics and could inform vaccine design. Lv et al. report a humanized monoclonal antibody that protected against SARS-CoV-2 in a mouse model. The cryo–electron microscopy structure, together with biochemical, cellular, and virological studies, showed that the antibody acts by binding to the receptor-binding domain of the spike and blocking its attachment to the host receptor. Science , this issue p. [1505][1] 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. [1]: /lookup/doi/10.1126/science.abc5881
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/295432
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Zhe Lv,Yong-Qiang Deng,Qing Ye,et al. Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody[J]. Science,2020.
APA	Zhe Lv.,Yong-Qiang Deng.,Qing Ye.,Lei Cao.,Chun-Yun Sun.,...&Xiangxi Wang.(2020).Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.Science.
MLA	Zhe Lv,et al."Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody".Science (2020).