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DOI | 10.1126/science.abf4830 |
Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody | |
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 | |
2021-02-19 | |
发表期刊 | Science |
出版年 | 2021 |
英文摘要 | As we continue to battle the COVID-19 pandemic, we must confront the possibility of new pathogenic coronaviruses emerging in humans in the future. With this in mind, Rappazzo et al. isolated antibodies from a survivor of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), used yeast display libraries to introduce diversity into these antibodies, and then screened for binding to SARS-CoV-2. One of the affinity-matured progeny strongly neutralized SARS-CoV-2, SARS-CoV, and two SARS-related viruses from bats. In addition, this antibody bound to the receptor-binding domains from a panel of sarbecoviruses, suggesting broader activity, and provided protection against SARS-CoV and SARS-CoV-2 in mouse models. Science , this issue p. [823][1] 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. [1]: /lookup/doi/10.1126/science.abf4830 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/315727 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | C. Garrett Rappazzo,Longping V. Tse,Chengzi I. Kaku,et al. Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody[J]. Science,2021. |
APA | C. Garrett Rappazzo.,Longping V. Tse.,Chengzi I. Kaku.,Daniel Wrapp.,Mrunal Sakharkar.,...&Laura M. Walker.(2021).Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.Science. |
MLA | C. Garrett Rappazzo,et al."Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody".Science (2021). |
条目包含的文件 | 条目无相关文件。 |
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