Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors.
Nat Chem Biol
; 18(11): 1270-1276, 2022 11.
Article
in English
| MEDLINE | ID: covidwho-2016763
ABSTRACT
Omicron and its subvariants have rendered most authorized monoclonal antibody-based treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ineffective, highlighting the need for biologics capable of overcoming SARS-CoV-2 evolution. These mostly ineffective antibodies target variable epitopes. Here we describe broad-spectrum SARS-CoV-2 inhibitors developed by tethering the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), to known non-neutralizing antibodies that target highly conserved epitopes in the viral spike protein. These inhibitors, called receptor-blocking conserved non-neutralizing antibodies (ReconnAbs), potently neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron. Neutralization potency is lost when the linker joining the binding and inhibitory ReconnAb components is severed. In addition, a bi-functional ReconnAb, made by linking ACE2 to a bi-specific antibody targeting two non-overlapping conserved epitopes, defined here, shows sub-nanomolar neutralizing activity against all VOCs, including Omicron and BA.2. Given their conserved targets and modular nature, ReconnAbs have the potential to act as broad-spectrum therapeutics against SARS-CoV-2 and other emerging pandemic diseases.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Biological Products
/
COVID-19 Drug Treatment
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Nat Chem Biol
Journal subject:
Biology
/
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
S41589-022-01140-1
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