Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.

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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Betacoronavirus, COVID-19, Coronavirus Infections, Cryoelectron Microscopy, Humans, Neutralization Tests, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Binding, Protein Conformation, Protein Domains, Receptors, Virus, SARS-CoV-2, Single-Domain Antibodies, Spike Glycoprotein, Coronavirus
Nat Commun
Date: Nov. 04, 2020
Download Curated Data For This Publication
245667
Switch View:
  • Interactions 2