Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein

• Published in: Cell Vol. 185; no. 13; pp. 2279 - 2291.e17
• Main Authors: Tortorici, M. Alejandra, Walls, Alexandra C., Joshi, Anshu, Park, Young-Jun, Eguia, Rachel T., Miranda, Marcos C., Kepl, Elizabeth, Dosey, Annie, Stevens-Ayers, Terry, Boeckh, Michael J., Telenti, Amalio, Lanzavecchia, Antonio, King, Neil P., Corti, Davide, Bloom, Jesse D., Veesler, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.06.2022
• Subjects: aminopeptidase; Animals; Cats; CCoV-HuPn-2018; CD13 Antigens - chemistry; CD13 Antigens - metabolism; Cell Line; children; Coronavirus - metabolism; Coronavirus 229E, Human - metabolism; Coronavirus Infections; cryo-EM; Dogs; glycoproteins; HCoV-229E; Humans; membrane alanyl aminopeptidase; monoclonal antibodies; oligosaccharides; Orthocoronavirinae; pathogens; Receptors, Virus - metabolism; sialosides; Spike Glycoprotein, Coronavirus - metabolism; Swine; therapeutics; vaccines; zoonotic viruses; ɑ-coronaviruses; ɑ-coronaviruses; HCoV-229E; zoonotic viruses; aminopeptidase; sialosides; CCoV-HuPn-2018; cryo-EM
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2022.05.019

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. [Display omitted] •Cryo-EM structures of CCoV-HuPn-2018 S reveal two conformational states of domain 0•Canine, feline, porcine APN orthologs mediate S-mediated entry•Engineering N739 glycan in human APN enables CCoV-HuPn-2018 entry•Plasma from HCoV-229E-infected subjects inhibit CCoV-HuPn-2018 S-mediated entry Cryo-EM structures of the coronavirus CCoV-HuPn-2018 S reveal two conformations of domain 0, which recognize sialosides. Canine, feline, and porcine APNs and human N739 glycan knockin APN are entry receptors, suggesting that SNPs might account for CCoV-HuPn-2018 detection in patients. Human antibodies elicited by coronavirus 229E infection inhibit CCoV-HuPn-2018, highlighting ɑ-coronavirus cross-neutralizing activity.