Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.
Science
; 375(6579): 449-454, 2022 Jan 28.
Article
in English
| MEDLINE | ID: covidwho-1723472
ABSTRACT
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
/
Broadly Neutralizing Antibodies
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Viral
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Science
Year:
2022
Document Type:
Article
Affiliation country:
Science.abm8143
Similar
MEDLINE
...
LILACS
LIS