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Rappazzo, C Garrett; Tse, Longping V; Kaku, Chengzi I; Wrapp, Daniel; Sakharkar, Mrunal; Huang, Deli; Deveau, Laura M; Yockachonis, Thomas J; Herbert, Andrew S; Battles, Michael B; O'Brien, Cecilia M; Brown, Michael E; Geoghegan, James C; Belk, Jonathan; Peng, Linghang; Yang, Linlin; Hou, Yixuan; Scobey, Trevor D; Burton, Dennis R; Nemazee, David; Dye, John M; Voss, James E; Gunn, Bronwyn M; McLellan, Jason S; Baric, Ralph S; Gralinski, Lisa E; Walker, Laura M
Science (American Association for the Advancement of Science), 02/2021, Letnik: 371, Številka: 6531Journal Article
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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Vir: Osebne bibliografije
in: SICRIS
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