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, 13, 14}

Show full list: 48 authors

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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

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

¹³

Frontiers Science Center for Cell Responses, Nankai University, Tianjin, 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

scimago Q1

SJR: 4.887

CiteScore: 24.9

Impact factor: 14.7

ISSN: 20411723

DOI: 10.1038/s41467-021-22926-2

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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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