The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
- University of Minnesota, United States
- University of Iowa, United States
- University of Texas Medical Branch, United States
- Lindsley F Kimball Research Institute, United States
- 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
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
- 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
- Received: November 11, 2020
- Preprint posted: November 17, 2020 (view preprint)
- Accepted: July 28, 2021
- Accepted Manuscript published: August 2, 2021 (version 1)
- 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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The Development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
eLife 10:e64815.
https://doi.org/10.7554/eLife.64815
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