7TAS

SARS-CoV-2 spike in complex with the S2K146 neutralizing antibody Fab fragment (local refinement of the RBD and S2K146)

7TAS の概要

• エントリーDOI: 10.2210/pdb7tas/pdb
• EMDBエントリー: 25783
• 分子名称: S2K146 Fab heavy chain, S2K146 Fab light chain, Spike glycoprotein, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, covid-19, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 167655.25

構造登録者

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2021-12-21, 公開日: 2022-01-12, 最終更新日: 2024-10-09)

主引用文献

Park, Y.J.,De Marco, A.,Starr, T.N.,Liu, Z.,Pinto, D.,Walls, A.C.,Zatta, F.,Zepeda, S.K.,Bowen, J.E.,Sprouse, K.R.,Joshi, A.,Giurdanella, M.,Guarino, B.,Noack, J.,Abdelnabi, R.,Foo, S.C.,Rosen, L.E.,Lempp, F.A.,Benigni, F.,Snell, G.,Neyts, J.,Whelan, S.P.J.,Virgin, H.W.,Bloom, J.D.,Corti, D.,Pizzuto, M.S.,Veesler, D.
Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.
Science, 375:449-454, 2022

PubMed Abstract: 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.

PubMed: 34990214
DOI: 10.1126/science.abm8143

実験手法

ELECTRON MICROSCOPY (3.2 Å)