1. Academic Validation
  2. Identification of potent human neutralizing antibodies against SARS-CoV-2 implications for development of therapeutics and prophylactics

Identification of potent human neutralizing antibodies against SARS-CoV-2 implications for development of therapeutics and prophylactics

  • Nat Commun. 2021 Aug 9;12(1):4887. doi: 10.1038/s41467-021-25153-x.
Shaojuan Zhao  # 1 2 Huajun Zhang  # 1 Xinglou Yang  # 1 Haiwei Zhang 1 Ying Chen 1 2 Yancheng Zhan 1 2 Xiaoqing Zhang 1 2 Rendi Jiang 1 2 Meiqin Liu 1 2 Lan Liu 1 Li Chen 1 2 Wei Tang 1 Cheng Peng 1 Xiaoxiao Gao 1 Zhe Zhang 1 Zhengli Shi 3 Rui Gong 4
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. zlshi@wh.iov.cn.
  • 4 CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. gongr@wh.iov.cn.
  • # Contributed equally.
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.

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