7A25

Cryo-EM structure of the SARS-CoV-2 spike protein bound to neutralizing sybodies (Sb23)

Summary for 7A25

• Entry DOI: 10.2210/pdb7a25/pdb
• EMDB information: 11616
• Descriptor: Spike glycoprotein, Sybody 23, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, complex, nanobody, spike, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 431465.25

Authors

Hallberg, B.M.,Das, H. (deposition date: 2020-08-16, release date: 2020-11-25)

Primary citation

Custodio, T.F.,Das, H.,Sheward, D.J.,Hanke, L.,Pazicky, S.,Pieprzyk, J.,Sorgenfrei, M.,Schroer, M.A.,Gruzinov, A.Y.,Jeffries, C.M.,Graewert, M.A.,Svergun, D.I.,Dobrev, N.,Remans, K.,Seeger, M.A.,McInerney, G.M.,Murrell, B.,Hallberg, B.M.,Low, C.
Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2.
Nat Commun, 11:5588-5588, 2020

PubMed 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 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.

PubMed: 33149112
DOI: 10.1038/s41467-020-19204-y

Experimental method

ELECTRON MICROSCOPY (3.06 Å)