OmniVira

Host range, transmissibility and antigenicity of a pangolin coronavirus.

Yixuan J Hou1,2 Shiho Chiba3 Sarah R Leist1 Rita M Meganck1 David R Martinez1 Alexandra Schäfer1 Nicholas J Catanzaro1 Vishwaraj Sontake4 Ande West1 Catlin E Edwards1 Boyd Yount1 Rhianna E Lee5 Samuel C Gallant5 Seth J Zost6 John Powers1 Lily Adams1 Edgar F Kong1 Melissa Mattocks1 Aleksandra Tata4 Scott H Randell5 Purushothama R Tata4 Peter Halfmann3 James E Crowe6 Yoshihiro Kawaoka3,7 Ralph S Baric8,9
Affiliations 9 institutions
  1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  2. Moderna Inc., Cambridge, MA, USA.
  3. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  4. Department of Cell Biology, Regeneration Next Initiative, Duke University Medical Center, Durham, NC, USA.
  5. Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  6. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  7. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  8. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
  9. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
PMID37749254 DOI10.1038/s41564-023-01476-x Year2023 Journal Nature microbiology Nat Microbiol Languageeng Statusppublish

Abstract

The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration approved drugs, and neutralized by COVID-19 patient sera and SARS-CoV-2 therapeutic antibodies in vitro. A pan-Sarbecovirus antibody and SARS-CoV-2 S2P recombinant protein vaccine protected BALB/c mice from PgCoV infection. In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody. Efficient PgCoV replication in primary human cells and hACE2 mice, coupled with a capacity for airborne spread, highlights an emergence potential. However, low competitive fitness, pre-immune humans and the benefit of COVID-19 countermeasures should impede its ability to spread globally in human populations.

Supporting text Virus Host Location
COVID-19 425 Severe acute respiratory syndrome-related coronavirus 78 Animals 1948 Antibodies, Viral 212 COVID-19 Vaccines 11 Cricetinae 41 Host Specificity 132 Humans 1440 Mice 253 Mice, Inbred BALB C 73 Pangolins 29 SARS-CoV-2 453

Evidence records

3 total
Experimental Infection
3 records · 3 evidence types
Evidence type Pathogenicity Experiment
1 records
OVE7378 Pathogenicity Experiment
Key finding

PgCoV infection caused severe clinical disease in K18-hACE2 mice under experimental challenge.

Virus
SARS-related coronavirus
Host
house mouse Mus musculus Experimental system
Location
Not specified
Supporting text

In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody.

Method
experimental infection | clinical observation of disease signs
Experimental system
K18-hACE2 mouse model
Evidence type Host Range Experiment
1 records
OVE7375 Host Range Experiment
Key finding

PgCoV replicated efficiently in primary human cells, demonstrating susceptibility of human-derived cells to infection.

Virus
SARS-related coronavirus
Host
primary human cells Homo sapiens Experimental system pangolins Manidae Natural host
Location
Not specified
Supporting text

In primary human cells, PgCoV replicated efficiently but with reduced fitness.

Method
cell culture infection | viral replication assay
Experimental system
primary human cell culture
Evidence type Experimental Transmission
1 records
OVE7376 Experimental Transmission
Key finding

PgCoV showed less efficient airborne transmission between hamsters compared with SARS-CoV-2 in a controlled experimental setup.

Virus
SARS-related coronavirus Severe acute respiratory syndrome coronavirus 2
Host
hamsters Cricetinae Experimental system
Location
Not specified
Supporting text

PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters.

Method
airborne transmission assay | comparative infection model in hamsters
Experimental system
airborne transmission animal model