A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants

Yanyun Du, Rui Shi, Ying Zhang, Xiaomin Duan, Li Li, Jing Zhang, Fengze Wang, Ruixue Zhang, Hao Shen, Yue Wang, Zheng Wu, Qianwen Peng, Ting Pan, Wanwei Sun, Weijin Huang, Yue Feng, Hui Feng, Junyu Xiao, Wenjie Tan (), Youchun Wang (), Chenhui Wang () and Jinghua Yan ()
Additional contact information
Yanyun Du: Huazhong University of Science and Technology
Rui Shi: Chinese Academy of Sciences
Ying Zhang: Peking University
Xiaomin Duan: Chinese Academy of Sciences
Li Li: Shanghai Junshi Biosciences Co., Ltd
Jing Zhang: Shanghai Junshi Biosciences Co., Ltd
Fengze Wang: Chinese Academy of Sciences
Ruixue Zhang: Peking University
Hao Shen: Peking University
Yue Wang: Chinese Academy of Sciences
Zheng Wu: Chinese Academy of Sciences
Qianwen Peng: Huazhong University of Science and Technology
Ting Pan: Huazhong University of Science and Technology
Wanwei Sun: Huazhong University of Science and Technology
Weijin Huang: National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals
Yue Feng: Beijing University of Chemical Technology
Hui Feng: Shanghai Junshi Biosciences Co., Ltd
Junyu Xiao: Peking University
Wenjie Tan: Chinese Center for Disease Control and Prevention
Youchun Wang: National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals
Chenhui Wang: Huazhong University of Science and Technology
Jinghua Yan: Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

Date: 2021
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DOI: 10.1038/s41467-021-25331-x

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