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Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.
- Source :
-
Nature communications [Nat Commun] 2020 Nov 04; Vol. 11 (1), pp. 5588. Date of Electronic Publication: 2020 Nov 04. - Publication Year :
- 2020
-
Abstract
- The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC <subscript>50</subscript> of 0.6 µg/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the 'up' ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses.
- Subjects :
- Angiotensin-Converting Enzyme 2
Antibodies, Monoclonal immunology
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
COVID-19
Cryoelectron Microscopy
Humans
Neutralization Tests
Protein Binding
Protein Conformation
Protein Domains immunology
Receptors, Virus metabolism
SARS-CoV-2
Betacoronavirus immunology
Coronavirus Infections prevention & control
Pandemics prevention & control
Peptidyl-Dipeptidase A metabolism
Pneumonia, Viral prevention & control
Single-Domain Antibodies immunology
Spike Glycoprotein, Coronavirus immunology
Spike Glycoprotein, Coronavirus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33149112
- Full Text :
- https://doi.org/10.1038/s41467-020-19204-y