Journal article
The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
eLIFE, Vol.10, e64815
08/01/2021
DOI: 10.7554/eLife.64815
PMCID: PMC8354634
PMID: 34338634
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.
Keywords: ACE2; COVID-19; animal model; crystal structures; drug pharmacokinetics; infectious disease; microbiology; single-chain antibody from camelids; spike protein receptor-binding domain; virus; virus neutralization.
© 2021, Ye et al.
Details
- Title: Subtitle
- The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates
- Creators
- Gang YeJoseph GallantJian ZhengChristopher MasseyKe ShiWanbo TaiAbby OdleMolly VickersJian ShangYushun WanLanying DuHideki AiharaStanley PerlmanAaron LeBeauFang Li
- Resource Type
- Journal article
- Publication Details
- eLIFE, Vol.10, e64815
- DOI
- 10.7554/eLife.64815
- PMID
- 34338634
- PMCID
- PMC8354634
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01AI157975; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01AI089728; DOI: 10.13039/100000002, name: National Institutes of Health, award: R35GM118047; DOI: 10.13039/100007249, name: University of Minnesota; DOI: 10.13039/100000892, name: Prostate Cancer Foundation
- Language
- English
- Date published
- 08/01/2021
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984125518802771
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