National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM120553
米国
引用
ジャーナル: Science / 年: 2022 タイトル: Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry. 著者: Young-Jun Park / Anna De Marco / Tyler N Starr / Zhuoming Liu / Dora Pinto / Alexandra C Walls / Fabrizia Zatta / Samantha K Zepeda / John E Bowen / Kaitlin R Sprouse / Anshu Joshi / Martina ...著者: Young-Jun Park / Anna De Marco / Tyler N Starr / Zhuoming Liu / Dora Pinto / Alexandra C Walls / Fabrizia Zatta / Samantha K Zepeda / John E Bowen / Kaitlin R Sprouse / Anshu Joshi / Martina Giurdanella / Barbara Guarino / Julia Noack / Rana Abdelnabi / Shi-Yan Caroline Foo / Laura E Rosen / Florian A Lempp / Fabio Benigni / Gyorgy Snell / Johan Neyts / Sean P J Whelan / Herbert W Virgin / Jesse D Bloom / Davide Corti / Matteo Samuele Pizzuto / David Veesler / 要旨: Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and ...Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.
全体 : SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody...
全体
名称: SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (local refinement of the RBD and S2K146)
要素
複合体: SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (local refinement of the RBD and S2K146)
複合体: SARS-CoV-2 spike
タンパク質・ペプチド: S2K146 Fab heavy chain
タンパク質・ペプチド: Spike glycoprotein
複合体: S2K146
タンパク質・ペプチド: S2K146 Fab light chain
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超分子 #1: SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody...
超分子
名称: SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (local refinement of the RBD and S2K146) タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Severe acute respiratory syndrome coronavirus 2 (ウイルス)