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Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain

Author

Listed:
  • Xiaojing Chi

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiuying Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Conghui Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xinhui Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xiang Li

    (Beijing Kawin Technology Co., Ltd.)

  • Jianhua Hou

    (Beijing Kawin Technology Co., Ltd.)

  • Lili Ren

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Qi Jin

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jianwei Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wei Yang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant (KD) of 0.99–35.5 nM. The monomeric sdAbs show half maximal neutralization concentration (EC50) of 0.0009–0.07 µg/mL and 0.13–0.51 µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies.

Suggested Citation

  • Xiaojing Chi & Xiuying Liu & Conghui Wang & Xinhui Zhang & Xiang Li & Jianhua Hou & Lili Ren & Qi Jin & Jianwei Wang & Wei Yang, 2020. "Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain," Nature Communications, Nature, vol. 11(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18387-8
    DOI: 10.1038/s41467-020-18387-8
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