9SBB

Monoclonal Antibodies from COVID-19 Convalescent Patients Target Cryptic Epitopes for Universal SARS-CoV-2 Neutralization

9SBB の概要

• エントリーDOI: 10.2210/pdb9sbb/pdb
• 分子名称: TAU-2310 Fab Heavy Chain, TAU-2310 Fab Light Chain, Spike protein S1, ... (8 entities in total)
• 機能のキーワード: immune complex, sars-cov-2, receptor binding domain, neutralizing antibody, viral protein
• 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: 72318.34

構造登録者

Dessau, M.,Harit, A. (登録日: 2025-08-08, 公開日: 2026-03-18, 最終更新日: 2026-04-08)

主引用文献

Harit, A.,Mor, M.,Yefet, R.,Izhaki-Tavor, L.S.,Gal-Tanamy, M.,Freund, N.T.,Dessau, M.
Monoclonal antibodies from COVID-19 convalescent patients target cryptic epitopes for broad SARS-CoV-2 neutralization.
Proc.Natl.Acad.Sci.USA, 123:e2523864123-e2523864123, 2026

PubMed Abstract: The COVID-19 pandemic, which has resulted in over seven million global fatalities, poses a substantial threat to public health and precipitated a global economic crisis. Emerging variants of concern (VOCs) with enhanced transmissibility and improved immune evasion may compromise the efficacy of current antiviral and immunotherapies, necessitating comprehensive investigations into the immune response to SARS-CoV-2. The conformational dynamics of the receptor binding domain in SARS-CoV-2 spike and the presentation of neutralizing antibody epitopes influence viral transmission and infection rates. In this study, we have identified highly conserved non-receptor-binding motif epitopes for two potent monoclonal antibodies (mAbs), TAU-1109 and TAU-2310, isolated from convalescent human patients, which contribute to the broad neutralizing activity of these mAbs against all the circulating VOCs, including the recently emerged Omicron subvariants. We employed high-resolution structural data in conjunction with systematic biochemical investigation to elucidate the neutralization mechanism of TAU-1109 and TAU-2310. The mechanism involves antibody-mediated destabilization of the spike trimer, resulting in the premature shedding of the S1 subunit and rendering the spike incapable of mediating host cell entry. The identification of conserved cryptic epitopes in our study advances the mechanistic understanding of immune response against SARS-CoV-2, providing alternative avenues for the development of universal therapeutic antibodies and vaccines to combat COVID-19.

PubMed: 41880581
DOI: 10.1073/pnas.2523864123

実験手法

X-RAY DIFFRACTION (2.12 Å)