8ZPP

Local CryoEM structure of the SARS-CoV-2 BA.5 in complex with ORB10 Fab

8ZPP の概要

• エントリーDOI: 10.2210/pdb8zpp/pdb
• EMDBエントリー: 60351
• 分子名称: Spike glycoprotein,Fibritin, variable heavy chain of ORB10 Fab, variable light chain of ORB10 Fab (3 entities in total)
• 機能のキーワード: sars-cov-2, antibody, complex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 164096.72

構造登録者

Cao, S.,Leng, C.,Hu, H. (登録日: 2024-05-30, 公開日: 2024-12-25, 最終更新日: 2025-07-16)

主引用文献

Hu, H.,Leng, C.,Shu, Y.,Peng, L.,Wu, F.,Liu, J.,Zhang, X.,Zhou, W.,Xiao, Q.,Li, Y.,Wu, B.,Shen, J.,Li, J.,Gong, R.,Yan, B.,Deng, F.,Hu, Z.,Cao, S.,Wang, M.
Structural insights into hybridoma-derived neutralizing monoclonal antibodies against Omicron BA.5 and XBB.1.16 variants of SARS-CoV-2.
J.Virol., 99:e0130724-e0130724, 2025

PubMed Abstract: The emergence of novel variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose an ongoing challenge for global public health services, highlighting the urgent need for effective therapeutic interventions. Neutralizing monoclonal antibodies (mAbs) are a major therapeutic strategy for the treatment of COVID-19 and other viral diseases. In this study, we employed hybridoma technology to generate mAbs that target the BA.5 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Through a comprehensive screening process, we identified four mAbs capable of effectively neutralizing BA.5, XBB.1.16, and related variant infections , among which ORB10 was found to neutralize BA.5 variants with a plaque reduction neutralization test (PRNT) of 8.7 ng/mL. Additionally, competitive binding assays, sequencing of heavy and light chain variable regions, and binding kinetics characterization provided insights into the epitopes and binding affinities of the identified mAbs. Moreover, experiments in the K18-hACE2 mouse model demonstrated the protective efficacy of ORB10 against both BA.5 and XBB.1.16 variants. Finally, cryo-electron microscopy structural analysis of the ORB10-RBD complex identified key residues involved in the antibody-antigen interactions, providing insights into the molecular mechanisms of neutralization and immune escape of SARS-CoV-2 Omicron variants from mAbs.

PubMed: 39772622
DOI: 10.1128/jvi.01307-24

実験手法

ELECTRON MICROSCOPY (3.6 Å)