Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody

CG Rappazzo, LV Tse, CI Kaku, D Wrapp, M Sakharkar… - Science, 2021 - science.org
Science, 2021science.org
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 severe acute respiratory syndrome coronavirus 2
(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 and neutralizes representative epidemic …
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 severe acute respiratory syndrome coronavirus 2 (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 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 that overlaps 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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