The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates

  1. Gang Ye
  2. Joseph Gallant
  3. Jian Zheng
  4. Christopher Massey
  5. Ke Shi
  6. Wanbo Tai
  7. Abby Odle
  8. Molly Vickers
  9. Jian Shang
  10. Yushun Wan
  11. Lanying Du Dr.
  12. Hideki Aihara
  13. Stanley Perlman
  14. Aaron LeBeau  Is a corresponding author
  15. Fang Li  Is a corresponding author
  1. University of Minnesota, United States
  2. University of Iowa, United States
  3. University of Texas Medical Branch, United States
  4. Lindsley F Kimball Research Institute, United States
  5. Lindsley F Kimball Research Institute, New York Blood Center, United States

Abstract

Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor ACE2. The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD ~3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus ~160 times more efficiently than ACE2 did. Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, Nanosota-1 may contribute to the battle against COVID-19.

Data availability

Coordinates and structure factors have been deposited to the Protein Data Bank with accession number 7KM5.

Article and author information

Author details

  1. Gang Ye

    Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, United States
    Competing interests
    Gang Ye, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6034-2174
  2. Joseph Gallant

    Pharmacology, University of Minnesota, Minneapolis, United States
    Competing interests
    Joseph Gallant, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4943-1744
  3. Jian Zheng

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    No competing interests declared.
  4. Christopher Massey

    Institutional Office of Regulated Nonclinical Studies, University of Texas Medical Branch, Galveston,, United States
    Competing interests
    No competing interests declared.
  5. Ke Shi

    Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States
    Competing interests
    No competing interests declared.
  6. Wanbo Tai

    New York Blood Center, Lindsley F Kimball Research Institute, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9864-8993
  7. Abby Odle

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    No competing interests declared.
  8. Molly Vickers

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    No competing interests declared.
  9. Jian Shang

    Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, United States
    Competing interests
    Jian Shang, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
  10. Yushun Wan

    Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, United States
    Competing interests
    Yushun Wan, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
  11. Lanying Du Dr.

    Viral Immunology Laboratory, Lindsley F Kimball Research Institute, New York Blood Center, New York, United States
    Competing interests
    No competing interests declared.
  12. Hideki Aihara

    Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7508-6230
  13. Stanley Perlman

    Microbiology and Immunology, University of Iowa, Iowa City, United States
    Competing interests
    No competing interests declared.
  14. Aaron LeBeau

    Pharmacology, University of Minnesota, Minneapolis, United States
    For correspondence
    alebeau@umn.edu
    Competing interests
    Aaron LeBeau, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
  15. Fang Li

    Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, United States
    For correspondence
    lifang@umn.edu
    Competing interests
    Fang Li, The University of Minnesota has filed a patent on Nanosota-1 drugs with F.L, G.Y., A.M.L., J.P.G., J.S., and Y.W. as inventors..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1958-366X

Funding

National Institutes of Health (R01AI157975)

  • Lanying Du Dr.
  • Stanley Perlman
  • Aaron LeBeau
  • Fang Li

National Institutes of Health (R01AI089728)

  • Fang Li

National Institutes of Health (R35GM118047)

  • Hideki Aihara

University of Minnesota

  • Fang Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. John W Schoggins, University of Texas Southwestern Medical Center, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Texas Medical Branch (protocol number 2007072), of the New York Blood Center (protocol number 194.22), of the University of Iowa (protocol number 9051795), and of the University of Minnesota (protocol number 2009-38426A).

Version history

  1. Received: November 11, 2020
  2. Preprint posted: November 17, 2020 (view preprint)
  3. Accepted: July 28, 2021
  4. Accepted Manuscript published: August 2, 2021 (version 1)
  5. Version of Record published: August 10, 2021 (version 2)

Copyright

© 2021, Ye et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Gang Ye
  2. Joseph Gallant
  3. Jian Zheng
  4. Christopher Massey
  5. Ke Shi
  6. Wanbo Tai
  7. Abby Odle
  8. Molly Vickers
  9. Jian Shang
  10. Yushun Wan
  11. Lanying Du Dr.
  12. Hideki Aihara
  13. Stanley Perlman
  14. Aaron LeBeau
  15. Fang Li
(2021)
The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
eLife 10:e64815.
https://doi.org/10.7554/eLife.64815

Share this article

https://doi.org/10.7554/eLife.64815

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