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Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants

  1. Author:
    Hong, Jessica
    Kwon, Hyung Joon [ORCID]
    Cachau,Raul
    Chen, Catherine Z [ORCID]
    Butay, Kevin John
    Duan, Zhijian
    Li, Dan
    Ren, Hua
    Liang, Tianyuzhou
    Zhu,Jianghai
    Dandey, Venkata P
    Martin, Negin P [ORCID]
    Esposito,Dom [ORCID]
    Ortega-Rodriguez, Uriel
    Xu, Miao
    Borgnia, Mario J [ORCID]
    Xie, Hang [ORCID]
    Ho, Mitchell [ORCID]

  2. Author Address

    Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891., Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993., Data Science and Information Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21702., National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850., Molecular Microscopy Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709., Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891., Viral Vector Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709., Protein Expression Laboratory, NCI RAS Initiative, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.,
    1. Year: 2022
    2. Date: May 03
    3. Epub Date: 2022 04 27
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 119
    2. 18
    3. Pages: e2201433119
  4. Type of Article: Article
  5. Article Number: e2201433119
  1. Abstract:

    SignificanceDue to their small size, nanobodies can recognize protein cavities that are not accessible to conventional antibodies. In this report, we built dromedary camel (Camelus dromedarius) VHH phage libraries for the isolation of high-affinity nanobodies that broadly neutralize SARS-CoV-2 variants. Cryo-EM complex structures reveal that one dromedary camel VHH nanobody (8A2) binds the S1 subunit of the viral spike protein, and the other (7A3) targets a deeply buried region that uniquely extends to the S2 subunit beyond the S1 subunit. These nanobodies can protect mice from the lethal challenge of variants B.1.351 or B.1.617.2, suggesting the therapeutic potential of these nanobodies against COVID-19. The dromedary camel VHH libraries could be helpful to isolate neutralizing nanobodies against future emerging viruses quickly.

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External Sources

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  2. DOI: 10.1073/pnas.2201433119
  3. PMID: 35476528

Library Notes

  1. Fiscal Year: FY2021-2022
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