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The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
- Source :
- eLife, Vol 10 (2021)
- Publication Year :
- 2021
- Publisher :
- eLife Sciences Publications, Ltd, 2021.
-
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 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.
- Subjects :
- Drug
Phage display
QH301-705.5
Science
media_common.quotation_subject
ACE2
Hamster
spike protein receptor-binding domain
Plasma protein binding
General Biochemistry, Genetics and Molecular Biology
Virus
crystal structures
In vivo
Biology (General)
single-chain antibody from camelids
media_common
General Immunology and Microbiology
biology
Chemistry
General Neuroscience
COVID-19
General Medicine
Virology
Viral Receptor
virus neutralization
biology.protein
Medicine
Antibody
Subjects
Details
- ISSN :
- 2050084X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....59a9184a86044d1159b0852daa3c9da8
- Full Text :
- https://doi.org/10.7554/elife.64815