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 Video
The importance of molecular interactions and stability in Gene Therapy
The importance of molecular interactions and stability in Gene Therapy

New advances in gene therapy have triggered a resurgence of interest in the field. Though gene therapy offe...

Up next
Isoform-Selective ATAD2 chemical probe with novel chemical structure and unusual mode of action
Isoform-Selective ATAD2 chemical probe with novel chemical structure and unusual mode of action

Have a question about Monolith?

Contact Specialist
×

Sign up to receive
the latest NanoTemper news, product updates, event announcements and more

First Name
Last Name
Company Name
Country
State
Province
State
Region
State
Canton
Agree to Subscribe & Privacy Policy*
*I have fully read, understood and agree to the Privacy Policy. I accept the storing and processing of my personal data by NanoTemper as described in the Privacy Policy.

By completing this form, you provide us consent to contact you with educational content, news and information about our products, services and events. You may unsubscribe at any time.
Thank you!
Error - something went wrong!