Broad and Potent Activity Against Sars-Like Viruses by an Engineered Human Monoclonal Antibody
National Technical Information Service; 2021.
Non-conventional
in English
| National Technical Information Service | ID: grc-753724
ABSTRACT
The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.
COVID-19; CORONAVIRUSES; ANTIBODIES; PATHOGENS; DISEASE OUTBREAKS; COUNTERMEASURES; THERAPY; NEUTRALIZATION; BLOOD PROTEINS; HYGIENE; PANDEMICS; MERS-COV; CLINICAL TRIALS; MUTATIONS; BIOPOLYMERS; RECEPTOR SITES (PHYSIOLOGY); AMINO ACIDS PEPTIDES AND PROTEINS; SARS; Sars-cov-2 antibodies; Rbds(receptor binding domains)
Full text:
Available
Collection:
Databases of international organizations
Database:
National Technical Information Service
Topics:
Variants
Language:
English
Year:
2021
Document Type:
Non-conventional
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