RT Journal Article
SR Electronic
T1 Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.23.165415
DO 10.1101/2020.06.23.165415
A1 Tânia F. Custódio
A1 Hrishikesh Das
A1 Daniel J Sheward
A1 Leo Hanke
A1 Samuel Pazicky
A1 Joanna Pieprzyk
A1 Michèle Sorgenfrei
A1 Martin Schroer
A1 Andrey Gruzinov
A1 Cy Jeffries
A1 Melissa Graewert
A1 Dmitri Svergun
A1 Nikolay Dobrev
A1 Kim Remans
A1 Markus A. Seeger
A1 Gerald M McInerney
A1 Ben Murrell
A1 B. Martin Hällberg
A1 Christian Löw
YR 2020
UL http://biorxiv.org/content/early/2020/06/23/2020.06.23.165415.abstract
AB 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 a novel 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.Competing Interest StatementThe authors have declared no competing interest.