9FR4

Structure of the SARS-CoV-2 spike glycoprotein in complex with nanobody 7F (local refinement)

9FR4 の概要

• エントリーDOI: 10.2210/pdb9fr4/pdb
• 関連するPDBエントリー: 9FR3
• EMDBエントリー: 50708
• 分子名称: Spike glycoprotein, Nanobody 7F (2 entities in total)
• 機能のキーワード: spike, coronavirus, nanobody, complex, sars2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 315151.56

構造登録者

Debski-Antoniak, O.,Hurdiss, D.L. (登録日: 2024-06-18, 公開日: 2025-03-19, 最終更新日: 2025-07-02)

主引用文献

Swart, I.C.,Debski-Antoniak, O.J.,Zegar, A.,de Bouter, T.,Chatziandreou, M.,van den Berg, M.,Drulyte, I.,Pyrc, K.,de Haan, C.A.M.,Hurdiss, D.L.,Bosch, B.J.,Oliveira, S.
A bivalent spike-targeting nanobody with anti-sarbecovirus activity.
J Nanobiotechnology, 23:196-196, 2025

PubMed Abstract: The continued emergence and zoonotic threat posed by coronaviruses highlight the urgent need for effective antiviral strategies with broad reactivity to counter new emerging strains. Nanobodies (or single-domain antibodies) are promising alternatives to traditional monoclonal antibodies, due to their small size, cost-effectiveness and ease of bioengineering. Here, we describe 7F, a llama-derived nanobody, targeting the spike receptor binding domain of sarbecoviruses and SARS-like coronaviruses. 7F demonstrates potent neutralization against SARS-CoV-2 and cross-neutralizing activity against SARS-CoV and SARS-like CoV WIV16 pseudoviruses. Structural analysis reveals 7F's ability to induce the formation of spike trimer dimers by engaging with two SARS-CoV-2 spike RBDs, targeting the highly conserved class IV region, though concentration dependent. Bivalent 7F constructs substantially enhance neutralization potency and breadth, up to more recent SARS-CoV-2 variants of concern. Furthermore, we demonstrate the therapeutic potential of bivalent 7F against SARS-CoV-2 in the fully differentiated 3D tissue cultures mirroring the epithelium of the human airway ex vivo. The broad sarbecovirus activity and distinctive structural features of bivalent 7F underscore its potential as promising antiviral against emerging and evolving sarbecoviruses.

PubMed: 40059135
DOI: 10.1186/s12951-025-03243-y

実験手法

ELECTRON MICROSCOPY (3.1 Å)