Open Access

Nature Communications, volume 12, issue 1, publication number 2623

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes

Yu Guo ¹

Lisu Huang ²

Guangshun Zhang ^{1, 3}

Yanfeng Yao ⁴

He Zhou ⁵

Shu-Huei Shen ⁶

Bingqing Shen ⁵

Bo Li ^{1, 3}

Xin Li ^{1, 3}

Qian Zhang ⁵

Mingjie Chen ⁵

Da Chen ^{1, 3}

Jia Wu ⁵

Dan Fu ¹

Xinxin Zeng ²

Mingfang Feng ⁵

Chunjiang Pi ⁵

Yuan Wang ^{1, 3}

Xingdong Zhou ^{1, 3}

Minmin Lu ⁵

Yarong Li ⁷

Yaohui Fang ⁶

Yun Yueh Lu ⁵

Xue Hu ⁶

Shanshan Wang ⁵

Wanju Zhang ²

Ge Gao ⁴

Francisco Adrian ⁵

Qisheng Wang ⁸

Feng Yu ⁸

Yun Peng ⁴

Alexander G. Gabibov ⁹

JUAN MIN ⁴

Yuhui Wang ^{1, 3}

HEYU HUANG ²

Gennady V Stepanov ⁹

Wei Zhang ^{1, 3}

Yan Cai ¹⁰

Junwei Liu ¹⁰

Zhiming Yuan ⁴

Chen Zhang ¹

Zhiyong Lou ¹¹

Fei Deng ⁶

Hongkai Zhang ^{1, 3, 12, 13}

Chao Shan ⁶

Liang Schweizer ⁵

Kun Sun ²

Z. Rao ^{1, 3, 12, 14}

Hide authors affiliations Show authors affiliations: 14 affiliations

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, People’s Republic of China |

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China |

College of Life Science, Nankai University, Tianjin, People’s Republic of China |

⁴

Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China |

⁵

HiFiBio (Hong Kong) Limited, Central, Hong Kong |

⁶

State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China |

⁷

Wuxi Biologics Limited, Shanghai, People’s Republic of China |

⁸

Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, People’s Republic of China |

⁹

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia |

¹⁰

Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin, People’s Republic of China |

¹¹

MOE Key Laboratory of Protein Science & Collaborative Innovation Center of Biotherapy, School of Medicine, Tsinghua University, Beijing, People’s Republic of China |

¹²

Frontiers Science Center for Cell Responses, Nankai University, Tianjin, People’s Republic of China |

¹³

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, People’s Republic of China |

¹⁴

Guangzhou Laboratory, Guangzhou, People’s Republic of China |

Publication type: Journal Article

Publication date: 2021-05-11

Springer Nature

Journal: Nature Communications

Quartile SCImago

Quartile WOS

Impact factor: 16.6

ISSN: 20411723, 20411723

DOI: 10.1038/s41467-021-22926-2

Copy DOI

General Chemistry

General Biochemistry, Genetics and Molecular Biology

General Physics and Astronomy

Abstract

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases. Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.

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International Journal of Molecular Sciences	International Journal of Molecular Sciences, 2, 2.9% International Journal of Molecular Sciences 2 publications, 2.9%
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Viruses	Viruses, 1, 1.45% Viruses 1 publication, 1.45%
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Cell Host and Microbe	Cell Host and Microbe, 1, 1.45% Cell Host and Microbe 1 publication, 1.45%
Bioorganic Chemistry	Bioorganic Chemistry, 1, 1.45% Bioorganic Chemistry 1 publication, 1.45%
Computers in Biology and Medicine	Computers in Biology and Medicine, 1, 1.45% Computers in Biology and Medicine 1 publication, 1.45%
Biosensors and Bioelectronics	Biosensors and Bioelectronics, 1, 1.45% Biosensors and Bioelectronics 1 publication, 1.45%
Immunity	Immunity, 1, 1.45% Immunity 1 publication, 1.45%
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PLoS Computational Biology	PLoS Computational Biology, 1, 1.45% PLoS Computational Biology 1 publication, 1.45%
ACS Infectious Diseases	ACS Infectious Diseases, 1, 1.45% ACS Infectious Diseases 1 publication, 1.45%
Bioinformatics Advances	Bioinformatics Advances, 1, 1.45% Bioinformatics Advances 1 publication, 1.45%
ACS Chemical Biology	ACS Chemical Biology, 1, 1.45% ACS Chemical Biology 1 publication, 1.45%
ACS applied materials & interfaces	ACS applied materials & interfaces, 1, 1.45% ACS applied materials & interfaces 1 publication, 1.45%
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Citations by publishers

	2 4 6 8 10 12 14
Springer Nature	Springer Nature, 13, 18.84% Springer Nature 13 publications, 18.84%
Elsevier	Elsevier, 13, 18.84% Elsevier 13 publications, 18.84%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 8, 11.59% Multidisciplinary Digital Publishing Institute (MDPI) 8 publications, 11.59%
Frontiers Media S.A.	Frontiers Media S.A., 6, 8.7% Frontiers Media S.A. 6 publications, 8.7%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 5, 7.25% Cold Spring Harbor Laboratory 5 publications, 7.25%
American Chemical Society (ACS)	American Chemical Society (ACS), 3, 4.35% American Chemical Society (ACS) 3 publications, 4.35%
Pleiades Publishing	Pleiades Publishing, 3, 4.35% Pleiades Publishing 3 publications, 4.35%
Acta Naturae Ltd	Acta Naturae Ltd, 2, 2.9% Acta Naturae Ltd 2 publications, 2.9%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 1.45% Public Library of Science (PLoS) 1 publication, 1.45%
Oxford University Press	Oxford University Press, 1, 1.45% Oxford University Press 1 publication, 1.45%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 1, 1.45% Royal Society of Chemistry (RSC) 1 publication, 1.45%
Taylor & Francis	Taylor & Francis, 1, 1.45% Taylor & Francis 1 publication, 1.45%
IEEE	IEEE, 1, 1.45% IEEE 1 publication, 1.45%
Wiley	Wiley, 1, 1.45% Wiley 1 publication, 1.45%
American Society for Microbiology	American Society for Microbiology, 1, 1.45% American Society for Microbiology 1 publication, 1.45%
Mary Ann Liebert	Mary Ann Liebert, 1, 1.45% Mary Ann Liebert 1 publication, 1.45%
Research Square Platform LLC	Research Square Platform LLC, 1, 1.45% Research Square Platform LLC 1 publication, 1.45%
The Russian Academy of Sciences	The Russian Academy of Sciences, 1, 1.45% The Russian Academy of Sciences 1 publication, 1.45%
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii	Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii, 1, 1.45% Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii 1 publication, 1.45%
	2 4 6 8 10 12 14

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Guo Yu. et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes // Nature Communications. 2021. Vol. 12. No. 1. 2623

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Guo Yu. et al. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes // Nature Communications. 2021. Vol. 12. No. 1. 2623

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TY - JOUR

DO - 10.1038/s41467-021-22926-2

UR - https://doi.org/10.1038/s41467-021-22926-2

TI - A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes

T2 - Nature Communications

AU - Guo, Yu

AU - Huang, Lisu

AU - Zhang, Guangshun

AU - Yao, Yanfeng

AU - Zhou, He

AU - Shen, Shu-Huei

AU - Shen, Bingqing

AU - Li, Bo

AU - Li, Xin

AU - Zhang, Qian

AU - Chen, Mingjie

AU - Chen, Da

AU - Wu, Jia

AU - Fu, Dan

AU - Zeng, Xinxin

AU - Feng, Mingfang

AU - Pi, Chunjiang

AU - Wang, Yuan

AU - Zhou, Xingdong

AU - Lu, Minmin

AU - Li, Yarong

AU - Fang, Yaohui

AU - Lu, Yun Yueh

AU - Hu, Xue

AU - Wang, Shanshan

AU - Zhang, Wanju

AU - Gao, Ge

AU - Adrian, Francisco

AU - Wang, Qisheng

AU - Yu, Feng

AU - Peng, Yun

AU - Gabibov, Alexander G.

AU - MIN, JUAN

AU - Wang, Yuhui

AU - HUANG, HEYU

AU - Stepanov, Gennady V

AU - Zhang, Wei

AU - Cai, Yan

AU - Liu, Junwei

AU - Yuan, Zhiming

AU - Zhang, Chen

AU - Lou, Zhiyong

AU - Deng, Fei

AU - Zhang, Hongkai

AU - Shan, Chao

AU - Schweizer, Liang

AU - Sun, Kun

AU - Rao, Z.

PY - 2021

DA - 2021/05/11 00:00:00

PB - Springer Nature

IS - 1

VL - 12

SN - 2041-1723

ER -

BibTex

Cite this

BibTex Copy

@article{2021_Guo,

author = {Yu Guo and Lisu Huang and Guangshun Zhang and Yanfeng Yao and He Zhou and Shu-Huei Shen and Bingqing Shen and Bo Li and Xin Li and Qian Zhang and Mingjie Chen and Da Chen and Jia Wu and Dan Fu and Xinxin Zeng and Mingfang Feng and Chunjiang Pi and Yuan Wang and Xingdong Zhou and Minmin Lu and Yarong Li and Yaohui Fang and Yun Yueh Lu and Xue Hu and Shanshan Wang and Wanju Zhang and Ge Gao and Francisco Adrian and Qisheng Wang and Feng Yu and Yun Peng and Alexander G. Gabibov and JUAN MIN and Yuhui Wang and HEYU HUANG and Gennady V Stepanov and Wei Zhang and Yan Cai and Junwei Liu and Zhiming Yuan and Chen Zhang and Zhiyong Lou and Fei Deng and Hongkai Zhang and Chao Shan and Liang Schweizer and Kun Sun and Z. Rao},

title = {A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes},

journal = {Nature Communications},

year = {2021},

volume = {12},

publisher = {Springer Nature},

month = {may},

url = {https://doi.org/10.1038/s41467-021-22926-2},

number = {1},

doi = {10.1038/s41467-021-22926-2}

}

Found error?

Publisher

Springer Nature

Journal

Nature Communications

Quartile SCImago

Quartile WOS

Impact factor

16.6

ISSN

20411723 (Print)
20411723 (Electronic)