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

November 4, 2020

Custódio, T., Das, H., Sheward, D., et al.

Nature Communications 2020, vol: 11 doi: 10.1038/s41467-020-19204-y

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.

View Publication

Topics: Prometheus, nanoDSF, Monolith - MST, Virology, Publications

Previous Article
Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody
Potent neutralization of clinical isolates of SARS-CoV-2 D614 and G614 variants by a monomeric, sub-nanomolar affinity nanobody

Up next
What these 3 publications uncovered about coronavirus protein structures using MST
What these 3 publications uncovered about coronavirus protein structures using MST

Coronaviruses (CoV) have been responsible for multiple outbreaks this century. The COVID-19 pandemic — caus...

Challenged by the complexity of
virus biology?

Biophysical methods can help.

Find out how