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| Title | Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. |
|---|---|
| Journal, issue, pages | Science, Vol. 371, Issue 6531, Page 823-829, Year 2021 |
| Publish date | Feb 19, 2021 |
 Authors | C 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 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 ...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 links | Science / PubMed:33495307 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 5.94 Å |
| Structure data |  EMDB-23160: |
| Source |
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Homo sapiens (human)
Severe acute respiratory syndrome coronavirus 2
