7UKM

Cryo-EM structure of Antibody 12-19 in complex with prefusion SARS-CoV-2 Spike glycoprotein

7UKM の概要

• エントリーDOI: 10.2210/pdb7ukm/pdb
• EMDBエントリー: 26583 26584
• 分子名称: Spike glycoprotein, 12-19 Fab Heavy Chain, 12-19 Fab Light Chain, ... (4 entities in total)
• 機能のキーワード: neutralizing antibody, viral fusion protein, sars-cov-2, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 516079.43

構造登録者

Casner, R.G.,Shapiro, L. (登録日: 2022-04-01, 公開日: 2023-10-04, 最終更新日: 2025-09-24)

主引用文献

Liu, L.,Casner, R.G.,Guo, Y.,Wang, Q.,Iketani, S.,Chan, J.F.,Yu, J.,Dadonaite, B.,Nair, M.S.,Mohri, H.,Reddem, E.R.,Yuan, S.,Poon, V.K.,Chan, C.C.,Yuen, K.Y.,Sheng, Z.,Huang, Y.,Bloom, J.D.,Shapiro, L.,Ho, D.D.
Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking.
Immunity, 56:2442-2455.e8, 2023

PubMed Abstract: SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

PubMed: 37776849
DOI: 10.1016/j.immuni.2023.09.003

実験手法

ELECTRON MICROSCOPY (3.03 Å)