9FR3

Structure of the SARS-CoV-2 spike glycoprotein in complex with nanobody 7F

Summary for 9FR3

• Entry DOI: 10.2210/pdb9fr3/pdb
• EMDB information: 50707
• Descriptor: Nanobody 7F, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: spike, coronavirus, nanobody, complex, sars2, viral protein
• Biological source: Lama glama; More
• Total number of polymer chains: 12
• Total formula weight: 954739.51

Authors

Debski-Antoniak, O.,Hurdiss, D.L. (deposition date: 2024-06-18, release date: 2025-03-19, Last modification date: 2025-07-02)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)