9DBE

Molecular basis of pathogenicity of the recently emerged FCoV-23 coronavirus. FCoV-23 S long domain 0 in swung-out conformation (local refinement)

Summary for 9DBE

• Entry DOI: 10.2210/pdb9dbe/pdb
• Related: 9DB3
• EMDB information: 46716
• Descriptor: FCoV-23 S long domain 0 in swung-out conformation (local refinement), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: coronavirus, alphacoronavirus, feline coronavirus, cryo-em, neutralization assays, binding assays, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• Biological source: Feline coronavirus
• Total number of polymer chains: 1
• Total formula weight: 165659.52

Authors

Tortorici, M.A.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2024-08-23, release date: 2025-07-09, Last modification date: 2025-07-23)

Primary citation

Tortorici, M.A.,Choi, A.,Gibson, C.A.,Lee, J.,Brown, J.T.,Stewart, C.,Joshi, A.,Harari, S.,Willoughby, I.,Treichel, C.,Leaf, E.M.,Bloom, J.D.,King, N.P.,Tait-Burkard, C.,Whittaker, G.R.,Veesler, D.
Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics.
Nature, 2025

PubMed Abstract: The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.

PubMed: 40634609
DOI: 10.1038/s41586-025-09155-z

Experimental method

ELECTRON MICROSCOPY (2.4 Å)