作者
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
发表日期
2021/2/19
期刊
Science
卷号
371
期号
6531
页码范围
823-829
出版商
American Association for the Advancement of Science
简介
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 …
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