OmniVira

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].
PMID35700730 DOI10.1016/j.cell.2022.05.019 Year2022 Journal Cell Languageeng Statusppublish

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.

Supporting text Virus Host Location
aminopeptidase 1 CCoV-HuPn-2018 2 cryo-EM 7 HCoV-229E 4 sialosides 1 zoonotic viruses 7 ɑ-coronaviruses 1 Coronavirus 92 Coronavirus 229E, Human 4 Coronavirus Infections 171 Animals 1948 Cats 120 CD13 Antigens 7 Cell Line 158 Dogs 176 Humans 1440 Receptors, Virus 204 Spike Glycoprotein, Coronavirus 274 Swine 258

Evidence records

5 total
Zoonotic Surveillance
3 records · 3 evidence types
Evidence type Virus Isolation
1 records
OVE6065 Virus Isolation
Key finding

The human coronavirus CCoV-HuPn-2018 was successfully isolated as infectious virus from a child's respiratory swab sample.

Virus
Alphacoronavirus
Host
human Homo sapiens Natural host
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.

Sample type
respiratory swab
Evidence type Viral Detection
1 records
OVE6070 Viral Detection
Key finding

Isolation of the canine-like coronavirus CCoV-HuPn-2018 from a human respiratory sample indicates an animal-to-human spillover event.

Virus
Alphacoronavirus
Host
dog Canis lupus familiaris Natural host human Homo sapiens Natural host
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
Evidence type Serological Evidence
1 records
OVE6069 Serological Evidence
Key finding

Human plasma antibodies from HCoV-229E infection and a porcine coronavirus monoclonal antibody neutralized CCoV-HuPn-2018 spike-mediated entry, demonstrating cross-reactive antibody activity among alpha-coronaviruses.

Virus
Alphacoronavirus human coronavirus 229E porcine coronavirus
Host
human Homo sapiens Natural host pig Sus scrofa Experimental system
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 assay | spike-mediated entry inhibition
Sample type
plasma | monoclonal antibody
Functional Mechanism
2 records · 1 evidence types
Evidence type Receptor Usage
2 records
OVE6066 Receptor Usage
Key finding

The CCoV-HuPn-2018 spike protein binds canine, feline, and porcine aminopeptidase N orthologs that serve as entry receptors.

Virus
Alphacoronavirus
Host
dog Canis lupus familiaris Experimental system cat family Felidae Experimental system pig Sus scrofa Experimental system
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
receptor-binding assay | cell-entry experiment
Receptors
aminopeptidase N | APN
OVE6067 Receptor Usage
Key finding

Structural analysis confirmed that the receptor-binding B domain of CCoV-HuPn-2018 spike interacts directly with canine aminopeptidase N.

Virus
Alphacoronavirus
Host
dog Canis lupus familiaris Experimental system
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
X-ray crystallography | structural complex determination
Receptors
aminopeptidase N | APN