Identification of potent human neutralizing antibodies against SARS-CoV-2 implications for development of therapeutics and prophylactics
Shaojuan Zhao,
Huajun Zhang,
Xinglou Yang,
Haiwei Zhang,
Ying Chen,
Yancheng Zhan,
Xiaoqing Zhang,
Rendi Jiang,
Meiqin Liu,
Lan Liu,
Li Chen,
Wei Tang,
Cheng Peng,
Xiaoxiao Gao,
Zhe Zhang,
Zhengli Shi () and
Rui Gong ()
Additional contact information
Shaojuan Zhao: Chinese Academy of Sciences
Huajun Zhang: Chinese Academy of Sciences
Xinglou Yang: Chinese Academy of Sciences
Haiwei Zhang: Chinese Academy of Sciences
Ying Chen: Chinese Academy of Sciences
Yancheng Zhan: Chinese Academy of Sciences
Xiaoqing Zhang: Chinese Academy of Sciences
Rendi Jiang: Chinese Academy of Sciences
Meiqin Liu: Chinese Academy of Sciences
Lan Liu: Chinese Academy of Sciences
Li Chen: Chinese Academy of Sciences
Wei Tang: Chinese Academy of Sciences
Cheng Peng: Chinese Academy of Sciences
Xiaoxiao Gao: Chinese Academy of Sciences
Zhe Zhang: Chinese Academy of Sciences
Zhengli Shi: Chinese Academy of Sciences
Rui Gong: Chinese Academy of Sciences
Nature Communications, 2021, vol. 12, issue 1, 1-11
Abstract:
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is spreading rapidly, which seriously impacts global public health and economy. Thus, developing effective drugs remains urgent. We identify two potent antibodies, nCoVmab1 and nCoVmab2, targeting the SARS-CoV-2 spike protein receptor-binding domain (RBD) with high affinities from a naïve human phage-displayed Fab library. nCoVmab1 and nCoVmab2 neutralize authentic SARS-CoV-2 with picomolar and nanomolar IC50 values, respectively. No detectable defects of nCoVmab1 and nCoVmab2 are found during the preliminary druggability evaluation. nCoVmab1 could reduce viral titer and lung injury when administered prophylactically and therapeutically in human angiotensin-converting enzyme II (hACE2)-transgenic mice. Therefore, phage display platform could be efficiently used for rapid development of neutralizing monoclonal antibodies (nmabs) with clinical potential against emerging infectious diseases. In addition, we determinate epitopes in RBD of these antibodies to elucidate the neutralizing mechanism. We also convert nCoVmab1 and nCoVmab2 to their germline formats for further analysis, which reveals the contribution of somatic hypermutation (SHM) during nCoVmab1 and nCoVmab2 maturation. Our findings not only provide two highly potent nmabs against SARS-CoV-2 as prophylactic and therapeutic candidates, but also give some clues for development of anti-SARS-CoV-2 agents (e.g., drugs and vaccines) targeting the RBD.
Date: 2021
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DOI: 10.1038/s41467-021-25153-x
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