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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.
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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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Full text: Available Collection: Databases of international organizations Database: National Technical Information Service Topics: Variants Language: English Year: 2021 Document Type: Non-conventional