Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.
Nat Struct Mol Biol
; 27(9): 846-854, 2020 09.
Article
in English
| MEDLINE | ID: covidwho-653285
ABSTRACT
The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Receptors, Virus
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Antibodies, Neutralizing
/
Pandemics
/
Single-Domain Antibodies
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
/
Antibodies, Viral
Type of study:
Randomized controlled trials
Language:
English
Journal:
Nat Struct Mol Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
S41594-020-0469-6
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