Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants-Reference-Cited by-同舟云学术

Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants

Published:2022-04-27 Issue:18 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Hong Jessica¹,Kwon Hyung Joon²^ORCID,Cachau Raul³,Chen Catherine Z.⁴^ORCID,Butay Kevin John⁵,Duan Zhijian⁶,Li Dan¹,Ren Hua¹,Liang Tianyuzhou¹,Zhu Jianghai³,Dandey Venkata P.⁵,Martin Negin P.⁷^ORCID,Esposito Dominic⁸^ORCID,Ortega-Rodriguez Uriel²,Xu Miao⁴,Borgnia Mario J.⁵^ORCID,Xie Hang²^ORCID,Ho Mitchell¹⁶^ORCID

Affiliation:

1. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891

2. 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

3. Data Science and Information Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21702

4. National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850

5. Molecular Microscopy Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

6. Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891

7. Viral Vector Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

8. Protein Expression Laboratory, NCI RAS Initiative, Frederick National Laboratory for Cancer Research, Frederick, MD 21702

Abstract

Significance Due 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 ) V H H 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 V H H 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 V H H libraries could be helpful to isolate neutralizing nanobodies against future emerging viruses quickly.

Funder

HHS | National Institutes of Health

HHS | NIH | National Cancer Institute

HHS | NIH | National Center for Advancing Translational Sciences

HHS | NIH | National Institute of Environmental Health Sciences

HHS | U.S. Food and Drug Administration

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2201433119