Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.
Nat Commun
; 11(1): 5588, 2020 11 04.
Article
in En
| MEDLINE
| ID: mdl-33149112
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 IC50 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Pandemics
/
Single-Domain Antibodies
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country: