1. Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein
- Author
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M. Alejandra Tortorici, Alexandra C. Walls, Anshu Joshi, Young-Jun Park, Rachel T. Eguia, Marcos C. Miranda, Elizabeth Kepl, Annie Dosey, Terry Stevens-Ayers, Michael J. Boeckh, Amalio Telenti, Antonio Lanzavecchia, Neil P. King, Davide Corti, Jesse D. Bloom, and David Veesler
- Subjects
Coronavirus ,Dogs ,Coronavirus 229E, Human ,Swine ,Spike Glycoprotein, Coronavirus ,Cats ,Animals ,Humans ,Receptors, Virus ,CD13 Antigens ,Coronavirus Infections ,General Biochemistry, Genetics and Molecular Biology ,Cell Line - 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.
- Published
- 2021