tetano
Editor, Senior Moderator
Nat Commun
. 2020 Nov 4;11(1):5588.
doi: 10.1038/s41467-020-19204-y.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
T?nia F Cust?dio[SUP] 1 [/SUP], Hrishikesh Das[SUP] 2 [/SUP], Daniel J Sheward[SUP] 3 4 [/SUP], Leo Hanke[SUP] 3 [/SUP], Samuel Pazicky[SUP] 1 [/SUP], Joanna Pieprzyk[SUP] 1 [/SUP], Mich?le Sorgenfrei[SUP] 5 [/SUP], Martin A Schroer[SUP] 6 [/SUP], Andrey Yu Gruzinov[SUP] 6 [/SUP], Cy M Jeffries[SUP] 6 [/SUP], Melissa A Graewert[SUP] 6 [/SUP], Dmitri I Svergun[SUP] 6 [/SUP], Nikolay Dobrev[SUP] 7 [/SUP], Kim Remans[SUP] 7 [/SUP], Markus A Seeger[SUP] 5 [/SUP], Gerald M McInerney[SUP] 3 [/SUP], Ben Murrell[SUP] 8 [/SUP], B Martin H?llberg[SUP] 9 10 [/SUP], Christian L?w[SUP] 11 [/SUP]
Affiliations
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 IC[SUB]50[/SUB] of 0.6 ?g/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.
. 2020 Nov 4;11(1):5588.
doi: 10.1038/s41467-020-19204-y.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
T?nia F Cust?dio[SUP] 1 [/SUP], Hrishikesh Das[SUP] 2 [/SUP], Daniel J Sheward[SUP] 3 4 [/SUP], Leo Hanke[SUP] 3 [/SUP], Samuel Pazicky[SUP] 1 [/SUP], Joanna Pieprzyk[SUP] 1 [/SUP], Mich?le Sorgenfrei[SUP] 5 [/SUP], Martin A Schroer[SUP] 6 [/SUP], Andrey Yu Gruzinov[SUP] 6 [/SUP], Cy M Jeffries[SUP] 6 [/SUP], Melissa A Graewert[SUP] 6 [/SUP], Dmitri I Svergun[SUP] 6 [/SUP], Nikolay Dobrev[SUP] 7 [/SUP], Kim Remans[SUP] 7 [/SUP], Markus A Seeger[SUP] 5 [/SUP], Gerald M McInerney[SUP] 3 [/SUP], Ben Murrell[SUP] 8 [/SUP], B Martin H?llberg[SUP] 9 10 [/SUP], Christian L?w[SUP] 11 [/SUP]
Affiliations
- PMID: 33149112
- 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 IC[SUB]50[/SUB] of 0.6 ?g/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.