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

Journal Article · · eLife
DOI:https://doi.org/10.7554/elife.64815· OSTI ID:1815011
 [1];  [2];  [3];  [4];  [5];  [6];  [3];  [3];  [1];  [1];  [6];  [5];  [3];  [7];  [1]
  1. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Veterinary and Biomedical Sciences. Center for Coronavirus Research
  2. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Pharmacology
  3. Univ. of Iowa, Iowa City, IA (United States). Dept. of Microbiology and Immunology
  4. Univ. of Texas Medical Branch, Galveston, TX (United States). Institutional Office of Regulated Nonclinical Studies
  5. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Biochemistry, Molecular Biology and Biophysics
  6. New York Blood Center, New York, NY (United States). Lab. of Viral Immunology. Lindsley F. Kimball Research Inst.
  7. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Pharmacology
+ Show Author Affiliations

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 angiotensin-converting enzyme 2 (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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1815011
Journal Information:
eLife, Journal Name: eLife Vol. 10; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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60 APPLIED LIFE SCIENCES
ACE2
COVID-19
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animal model
crystal structures
drug pharmacokinetics
single-chain antibody from camelids
spike protein receptor-binding domain
virus neutralization