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High Affinity Nanobodies Block SARS-CoV-2 Spike Receptor Binding Domain Interaction with Human Angiotensin Converting Enzyme

Thomas J. Esparza, Negin P. Martin, George P. Anderson, Ellen R. Goldman, David L. Brody
doi: https://doi.org/10.1101/2020.07.24.219857
Thomas J. Esparza
1The National Institute of Neurological Disorders and Stroke Intramural Research Program, Laboratory of Functional and Molecular Imaging, Bethesda, MD, USA 20892
2Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA 20892
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Negin P. Martin
3Viral Vector Core, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC, USA 27709
4Neurobiology Laboratory, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC, USA 27709
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George P. Anderson
5US Naval Research Laboratory, Center for Biomolecular Science and Engineering, Washington, DC, USA 20375
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Ellen R. Goldman
5US Naval Research Laboratory, Center for Biomolecular Science and Engineering, Washington, DC, USA 20375
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David L. Brody
1The National Institute of Neurological Disorders and Stroke Intramural Research Program, Laboratory of Functional and Molecular Imaging, Bethesda, MD, USA 20892
6Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA 20814
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  • For correspondence: david.brody@nih.gov
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ABSTRACT

There are currently no approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that are amenable to inexpensive large-scale production and can be delivered by inhalation. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1-5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 micrograms/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding: National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program, Uniformed Services University of the Health Sciences; National Institute of Environmental Health Sciences Intramural Research Program, Research Triangle Park, NC

  • Disclaimer: The views expressed in this manuscript reflect those of the authors, and not those of the Uniformed Services University of the Health Sciences or the Department of Defense.

  • additional data, analyses and discussion

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 23, 2020.
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High Affinity Nanobodies Block SARS-CoV-2 Spike Receptor Binding Domain Interaction with Human Angiotensin Converting Enzyme
Thomas J. Esparza, Negin P. Martin, George P. Anderson, Ellen R. Goldman, David L. Brody
bioRxiv 2020.07.24.219857; doi: https://doi.org/10.1101/2020.07.24.219857
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High Affinity Nanobodies Block SARS-CoV-2 Spike Receptor Binding Domain Interaction with Human Angiotensin Converting Enzyme
Thomas J. Esparza, Negin P. Martin, George P. Anderson, Ellen R. Goldman, David L. Brody
bioRxiv 2020.07.24.219857; doi: https://doi.org/10.1101/2020.07.24.219857

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