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Literature detail

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

M Alejandra Tortorici1 Alexandra C Walls2,3 Anshu Joshi1 Young-Jun Park1 Rachel T Eguia4 Marcos C Miranda2,5 Elizabeth Kepl2,5 Annie Dosey2,5 Terry Stevens-Ayers6 Michael J Boeckh6 Amalio Telenti7 Antonio Lanzavecchia8,9 Neil P King2,5 Davide Corti9 Jesse D Bloom4 David Veesler2,10
Affiliations 10 institutions
  1. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  2. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
  3. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
  4. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  5. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  6. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  7. Vir Biotechnology, San Francisco, CA 94158, USA.
  8. Istituto Nazionale Genetica Molecolare, 20122 Milano, Italy
  9. Humabs Biomed SA-a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  10. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: [email protected].
PMID 35700730 2022 Cell eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

aminopeptidase CCoV-HuPn-2018 cryo-EM HCoV-229E sialosides zoonotic viruses ɑ-coronaviruses Coronavirus Coronavirus 229E, Human Coronavirus Infections Animals Cats CD13 Antigens Cell Line Dogs Humans Receptors, Virus Spike Glycoprotein, Coronavirus

Structured evidence records

Evidence records

8 total
Receptor Usage 3 records
Receptor Usage Extraction confidence 1.00
Key finding

The CCoV-HuPn-2018 spike glycoprotein binds canine, feline, and porcine aminopeptidase N orthologs as entry receptors, showing receptor compatibility across species and structural complex formation with canine APN.

Location
Not specified
Supporting text

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.

Method
structural analysis
Receptors
aminopeptidase N (APN)
Receptor Usage Extraction confidence 1.00
Key finding

A glycosylation site introduced at position N739 of human aminopeptidase N enables CCoV-HuPn-2018 spike-mediated entry, indicating that minor receptor modifications can confer compatibility with human cells.

Location
Not specified
Supporting text

The introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry.

Method
cell-entry assay
Receptors
aminopeptidase N (APN)
Receptor Usage Extraction confidence 1.00
Key finding

The domain 0 of the CCoV-HuPn-2018 spike glycoprotein recognizes sialosides, suggesting a potential role in receptor attachment or host cell interaction.

Host
Not specified
Location
Not specified
Supporting text

We determined that its domain 0 recognizes sialosides.

Method
structural analysis
Receptors
sialosides
Cross Species Transmission 2 records
Cross Species Transmission Extraction confidence 0.90
Key finding

CCoV-HuPn-2018 spike protein interacts with APN receptors from dogs, cats, and pigs, supporting potential cross-species transmission among these animal hosts.

Location
Not specified
Supporting text

We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors.

Method
structural determination; binding assay
Study design
molecular receptor analysis
Transmission direction
animal-to-animal
Cross Species Transmission Extraction confidence 0.90
Key finding

CCoV-HuPn-2018 spike binding to porcine APN supports possible canine-to-pig cross-species transmission.

Location
Not specified
Supporting text

We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors.

Method
structural determination; binding assay
Study design
molecular receptor analysis
Transmission direction
animal-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The CCoV-HuPn-2018 spike glycoprotein binds aminopeptidase N receptors from multiple animal species, and a specific glycosylation site (N739) on human APN enables spike-mediated cell entry, indicating receptor adaptation enabling cross-species infection.

Host
Not specified
Location
Not specified
Supporting text

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.

Genes or proteins
spike; aminopeptidase N
Receptors
aminopeptidase N
Mutations
N739 glycosylation site
Mechanism types
receptor_binding; cell_entry; host_range_expansion
Serological Evidence 1 records
Serological Evidence Extraction confidence 0.80
Key finding

Cross-neutralizing antibodies derived from human and porcine coronavirus infections inhibited CCoV-HuPn-2018 spike-mediated viral entry, showing serological evidence of cross-species antibody activity.

Location
Not specified
Supporting text

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.

Method
neutralization test
Sample type
plasma
Spillover Event 1 records
Spillover Event Extraction confidence 0.95
Key finding

CCoV-HuPn-2018, related to canine coronaviruses, was isolated from a human, documenting an animal-to-human spillover.

Location
Not specified
Supporting text

The isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated.

Method
virus isolation; structural analysis
Study design
virus isolation
Transmission direction
animal-to-human