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PreprintCC BYbioRxiv

Mechanism of spike opening in a mammalian gammacoronavirus

  • J. D. Clarke
  • M. Grabias
  • A. Di Maio
  • H. Phlora
  • S. Vasiljevic
  • S. A. Burnap
  • R. Tripathy
  • W. Chai
  • W. B. Struwe
  • D. J. Benton
  • Y. Liu
  • S. J. Gamblin
1 more authors
  • A. G. Wrobel1
  1. 1University of Oxford, Department of Biochemistry
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Abstract

Coronavirus spike proteins mediate receptor binding and fusion and are key determinants of viral host range. To bind protein receptors, some CoV spikes undergo conformational changes termed opening, which expose the receptor-binding surface. Yet, the prerequisites and mechanism of spike opening remain poorly understood, especially outside of beta-CoVs, and many CoV spikes have been observed only in the closed conformation. The receptor specificities of gamma-CoVs, for which birds are natural hosts, await in-depth characterisation and their spikes have not been observed to open. Here, we report structures of the spike from an unusual mammalian gamma-CoV isolated from a beluga whale (BwCoV), in closed and open conformations, the latter with two S1B domains erect. BwCoV spike opening is associated with changes throughout S1 that resemble those observed in beta-CoV spikes and similarly propagate into destabilisation of the fusogenic S2 core. Furthermore, the BwCoV-S structure contains an additional density likely corresponding to a fatty acid, consistent with lipid binding stabilising the closed conformation through a pocket distinct from that identified for beta-CoVs. These structural insights reveal conserved principles regulating spike dynamics across coronavirus genera and support lipid binding as a potential modulatory mechanism of spike opening.

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Cite

BibTeXRIS
BibTeX
@misc{clarke2026mechanism,
  title = {{Mechanism of spike opening in a mammalian gammacoronavirus}},
  author = {J. D. Clarke and M. Grabias and A. Di Maio and H. Phlora and S. Vasiljevic and S. A. Burnap and R. Tripathy and W. Chai and W. B. Struwe and D. J. Benton and Y. Liu and S. J. Gamblin and A. G. Wrobel},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.30.755498},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755498v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Mechanism of spike opening in a mammalian gammacoronavirus
AU  - J. D. Clarke
AU  - M. Grabias
AU  - A. Di Maio
AU  - H. Phlora
AU  - S. Vasiljevic
AU  - S. A. Burnap
AU  - R. Tripathy
AU  - W. Chai
AU  - W. B. Struwe
AU  - D. J. Benton
AU  - Y. Liu
AU  - S. J. Gamblin
AU  - A. G. Wrobel
PY  - 2026
DA  - 2026/09/30
PB  - bioRxiv
DO  - 10.64898/2026.09.30.755498
UR  - https://www.biorxiv.org/content/10.64898/2026.09.30.755498v1
AB  - Coronavirus spike proteins mediate receptor binding and fusion and are key determinants of viral host range. To bind protein receptors, some CoV spikes undergo conformational changes termed opening, which expose the receptor-binding surface. Yet, the prerequisites and mechanism of spike opening remain poorly understood, especially outside of beta-CoVs, and many CoV spikes have been observed only in the closed conformation. The receptor specificities of gamma-CoVs, for which birds are natural hosts, await in-depth characterisation and their spikes have not been observed to open. Here, we report structures of the spike from an unusual mammalian gamma-CoV isolated from a beluga whale (BwCoV), in closed and open conformations, the latter with two S1B domains erect. BwCoV spike opening is associated with changes throughout S1 that resemble those observed in beta-CoV spikes and similarly propagate into destabilisation of the fusogenic S2 core. Furthermore, the BwCoV-S structure contains an additional density likely corresponding to a fatty acid, consistent with lipid binding stabilising the closed conformation through a pocket distinct from that identified for beta-CoVs. These structural insights reveal conserved principles regulating spike dynamics across coronavirus genera and support lipid binding as a potential modulatory mechanism of spike opening.
ER  -