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Cell
. 2022 May 27;S0092-8674(22)00650-X.
doi: 10.1016/j.cell.2022.05.019. Online ahead of print.
Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein
M Alejandra Tortorici 1 , Alexandra C Walls 2 , Anshu Joshi 1 , Young-Jun Park 1 , Rachel T Eguia 3 , Marcos C Miranda 4 , Elizabeth Kepl 4 , Annie Dosey 4 , Terry Stevens-Ayers 5 , Michael J Boeckh 5 , Amalio Telenti 6 , Antonio Lanzavecchia 7 , Neil P King 4 , Davide Corti 8 , Jesse D Bloom 3 , David Veesler 9
Affiliations
- PMID: 35700730
- DOI: 10.1016/j.cell.2022.05.019
Abstract
The isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. We determined the structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and showed that its domain 0 recognizes sialosides. We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors, and determined the structure of the receptor-binding B domain in complex with canine APN. The introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single-nucleotide polymorphisms might account for viral detection in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 spike-mediated entry, underscoring the cross-neutralizing activity among ɑ-coronaviruses. These data pave the way for vaccine and therapeutic development targeting this zoonotic pathogen representing the eighth human-infecting coronavirus.
Keywords: CCoV-HuPn-2018; HCoV-229E; aminopeptidase; cryo-EM; sialosides; zoonotic viruses; ɑ-coronaviruses.