An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction.
Nat Commun
; 11(1): 4420, 2020 09 04.
Article
in English
| MEDLINE | ID: covidwho-744371
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the 'up' and 'down' conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Camelids, New World
/
Angiotensin-Converting Enzyme Inhibitors
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Single-Domain Antibodies
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2020
Document Type:
Article
Affiliation country:
S41467-020-18174-5
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