Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Cell
; 181(5): 1004-1015.e15, 2020 05 28.
Article
in English
| MEDLINE | ID: covidwho-88549
ABSTRACT
Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
Single-Domain Antibodies
/
Betacoronavirus
Type of study:
Randomized controlled trials
Limits:
Animals
Language:
English
Journal:
Cell
Year:
2020
Document Type:
Article
Affiliation country:
J.cell.2020.04.031
Similar
MEDLINE
...
LILACS
LIS