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TitleBroad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.
Journal, issue, pagesScience, Vol. 371, Issue 6531, Page 823-829, Year 2021
Publish dateFeb 19, 2021
AuthorsC Garrett Rappazzo / Longping V Tse / Chengzi I Kaku / Daniel Wrapp / Mrunal Sakharkar / Deli Huang / Laura M Deveau / Thomas J Yockachonis / Andrew S Herbert / Michael B Battles / Cecilia M O'Brien / Michael E Brown / James C Geoghegan / Jonathan Belk / Linghang Peng / Linlin Yang / Yixuan Hou / Trevor D Scobey / Dennis R Burton / David Nemazee / John M Dye / James E Voss / Bronwyn M Gunn / Jason S McLellan / Ralph S Baric / Lisa E Gralinski / Laura M Walker /
PubMed AbstractThe 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 ...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.
External linksScience / PubMed:33495307 / PubMed Central
MethodsEM (single particle)
Resolution5.94 Å
Structure data

EMDB-23160:
Prefusion-stabilized SARS-CoV-2 spike bound by the engineered human antibody ADG-2
Method: EM (single particle) / Resolution: 5.94 Å

Source
  • Homo sapiens (human)
  • Severe acute respiratory syndrome coronavirus 2

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