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Animal Models and Resources for Coronavirus Research
The National Institutes of Health (NIH) Office of Research and Infrastructure Programs (ORIP) aims to provide investigators with the resources and infrastructure they need to improve human health, including by supporting the development of animal models of human disease. The current coronavirus disease 2019 (COVID-19) pandemic in humans, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, has compelled scientists around the world to work remarkably fast to develop vaccines and therapeutics using animal models. This page offers information and resources for investigators using animal models to study SARS-CoV-2 and other coronaviruses, including SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) that led to significant outbreaks during the early 2000s and mid-2010s, respectively.
- Susceptible Animal Species and Animal Models for Coronavirus Research
- ORIP, NIH and Other Resources for Coronaviruses Research
- Updates and Current Research from ORIP Grantees
- National Primate Research Centers and other Primate Resources
- Mutant Mouse Research and Resources Centers and other Rodent Resources
- Other ORIP Grantees
- Other Tools and Resources
Susceptible Animal Species and Animal Models for Coronavirus Research
For a given disease, such as COVID-19, researchers strive to develop animal models that mimic the human course of the disease. Animal models of human disease should have a route of infection, severity of disease, and morbidity and mortality levels that are similar to the human course of the disease.
Animals that are susceptible to or have been used as animal models to study SARS-CoV-2 include cat, ferret, fruit bat, hACE2 mouse, hamster, nonhuman primate, and tree shrew. Figure 1 below illustrates the host range of SARS-CoV-2 and the animals susceptible to SARS-CoV-2 infection, and Table 1 provides information and references on these animals.
Animal models that are susceptible to or have been used as animal models to study other coronaviruses include chicken, dog, duck, hACE2 mouse, hDPP4 mouse, lung-only mouse, and pig. Table 2 below provides information and references on these animals.
Figure 1. Host range of SARS-CoV-2 and animals susceptible to SARS-CoV-2. (From: Hossain MG, Javed A, Akter S, et al. SARS-CoV-2 host diversity: An update of natural infections and experimental evidence. J Microbiol Immunol Infect 2020;S1684-1182(20)30147-X. doi:10.1016/j.jmii.2020.06.006.)
Table 1. Animal species susceptible to SARS-CoV-2 infection
Animal | Mode of Transmission | Select References |
---|---|---|
cat |
respiratory tract, rectal swab, airborne |
|
ferret |
respiratory tract, rectal swab, contact, airborne |
|
fruit bat |
respiratory tract, contact |
|
hACE2 mouse |
respiratory tract, fecal swab |
|
hamster |
respiratory tract, rectal swab, contact |
|
nonhuman primate |
respiratory tract, contact, airborne |
|
tree shrew |
respiratory tract, fecal swab |
|
Table 2. Animal species susceptible to other coronaviruses
Animal | Coronavirus | Select References |
---|---|---|
chicken |
infectious bronchitis virus (IBV) |
|
dog |
SARS-CoV, canine coronavirus (CCoV) |
|
duck |
novel duck coronavirus |
|
hACE2 mouse |
SARS-CoV |
|
hDPP4 mouse |
MERS-CoV |
|
lung-only mouse |
MERS-CoV |
|
pig |
porcine deltacoronavirus (PDCoV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV) |
|
Select References—Animal Models for Coronavirus Research
- Abdel-Moneim AS, Abdelwhab, EM. Evidence for SARS-CoV-2 infection of animal hosts. Pathogens 2020;9(7):E529. doi: 10.3390/pathogens9070529.
- Hossain MG, Javed A, Akter S, et al. SARS-CoV-2 host diversity: An update of natural infections and experimental evidence. J Microbiol Immunol Infect 2020;S1684-1182(20)30147-X. doi: 10.1016/j.jmii.2020.06.006.
- Lakdawala SS, Menachery VD. The search for a COVID-19 animal model. Science 2020;368(6494):942–3. doi: 10.1126/science.abc6141.
- Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science 2020;368(6494):1016–20. doi: 10.1126/science.abb7015.
- Wu C, Zheng M, Yang Y, et al. In silico analysis of intermediate hosts and susceptible animals of SARS-CoV-2. ChemRxiv. doi: 10.26434/chemrxiv.12057996.v1.
- Song Z, Xu Y, Bao L, et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 2019;11(1):59. doi: 10.3390/v11010059.
- Gretebeck LM, Subbarao K. Animal models for SARS and MERS coronaviruses. Curr Opin Virol 2015;13:123–9. doi: 10.1016/j.coviro.2015.06.009.
ORIP, NIH and Other Resources for Coronaviruses Research
ORIP and the NIH have a range of resources available to assist the biomedical community in its research to combat coronaviruses. The resources below include general information, links to details on animal models and their uses, and references.
Nonhuman Primates
Nonhuman primate models available for the study of coronaviruses are listed at https://orip.nih.gov/non-human-primate-models.
The NPRCs are an ORIP-sponsored national network of seven facilities that together serve as a national scientific resource that provides animals, expertise, and specialized facilities and equipment to scientists conducting research with nonhuman primates.
Information from the NPRCs:
- NPRCs for the general public: nprc.org
- NPRCs for researchers: nprcresearch.org
- NPRCs’ COVID-19 research: nprc.org/research/nprcs-begin-covid-19-research
- NPRC Pathogen Detection Working Group’s SARS-CoV-2 testing: openresearch.labkey.com/project/National%20Primate%20Research%20Centers%20Pathogen%20Detection%20Working%20Group/begin.view?
- Tulane NPRC’s coronavirus research program: globalbiodefense.com/2020/02/21/tulane-national-primate-research-launches-coronavirus-research-program/
For general information on ORIP’s nonhuman primate resources, see ORIP’s Nonhuman Primate Resources fact sheet.
Select References—Nonhuman Primates
- Chandrashekar A, Liu J, Martinot AJ, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020;eabc4776. doi: 10.1126/science.abc4776.
- Deng W, Bao L, Liu J, et al. Primary exposure to SARS-CoV-2 protections against reinfection in rhesus macaques. Science 2020;eabc5343. doi: 10.1126/science.abc5343.
- Rockx B, Kuiken T, Herfst S, et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 2020;368(6494):1012–15. doi: 10.1126/science.abb7314.
- Yu J, Tostanoski LH, Peter L, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 2020;eabc6284. doi: 10.1126/science.abc6284.
COVID-19 research using monkeys: www.eara.eu/post/monkeys-in-covid‑19
Rodents
Mouse models available for COVID-19 research are listed at www.mmrrc.org/catalog/covid_models.php.
The MMRRC is an ORIP-sponsored consortium that distributes and cryopreserves genetically engineered mouse strains and mouse embryonic stem cell lines. The MMRRC’s four distribution facilities—together with its Informatics, Coordination and Service Center—function as a single repository that distributes animals to the scientific community at cost. Information on these facilities and their resources is available at www.mmrrc.org.
For general information on ORIP’s rodent resources, see ORIP’s Rodent Resources fact sheet or visit the ORIP Rodent Resources page.
Select References—Rodents
- Li K, McCray Jr. PB. Development of a mouse-adapted MERS coronavirus. 2020. In: Vijay R. (ed.) MERS Coronavirus: Methods and Protocols. Methods in Molecular Biology, vol. 2099. Humana, New York, NY. doi: 10.1007/978-1-0716-0211-9_13.
- Iwata-Yoshikawa N, Okamura T, Shimizu Y, et al. Acute respiratory infection in human dipeptidyl peptidase 4-transgenic mice infected with Middle East respiratory syndrome coronavirus. J Virol 2019;93(6):e01818-18. doi: 10.1128/JVI.01818-18.
- Wahl A, De C, Fernandez MA, et al. Precision mouse models with expanded tropism for human pathogens. Nat Biotechnol 2019;37(10):1163–73. doi: 10.1038/s41587-019-0225-9.
- Li K, Wohlford-Lenane CL, Channappanavar R, et al. Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice. Proc Natl Acad Sci U S A 2017;114(15):E3119–28. doi: 10.1073/pnas.1619109114.
- McCray Jr. PB, Pewe L, Wohlford-Lenane C, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 2007;81(2):813–21. doi: 10.1128/JVI.02012-06.
Information on mouse strains used to study coronaviruses, genes associated with coronavirus infection and pathology, and other resources, is available at www.informatics.jax.org/mgihome/other/coronavirus.shtml.
Chickens can be affected by a gammacoronavirus called infectious bronchitis virus (IBV), a highly contagious upper respiratory tract disease. IBV can be transmitted through bird-to-bird contact via respiratory secretions or droppings or through exposure to fomites (e.g., equipment, clothing). IBV is not transmittable from hen to chick through the egg.
The National Swine Resource and Research Center (NSRRC) serves as a central resource for reagents, creation of new genetically modified swine, and information and training related to use of pig models in biomedical research. Information is available at nsrrc.missouri.edu.
Pigs and humans share most physiological, biochemical, and anatomical features related to the lungs. The University of Illinois has been using swine to test emergency reconfigurations of ventilators for COVID-19 patients.
Pigs may be useful as a model for SARS-CoV-2 if the human ACE2 gene is introduced. Additionally, it has been suggested that SARS-CoV-2 requires additional proteins to facilitate virus entry or priming. Transmembrane serine protease 2 (TMPRSS2) may be required for viral processing, and the NSRRC has already produced pigs with TMPRSS2 knocked out. The NSRRC now proposes a model that can be crossed with existing lines to directly test the role of TMPRSS2. In addition to TMPRSS2, it is thought that glutamyl aminopeptidase (ENPEP), dipeptidyl peptidase 4 (DPP4), and alanyl aminopeptidase (ANPEP) may be required for SARS viruses. Researchers at the University of Missouri already have produced ANPEP knockout swine (see Table 2); ANPEP is required by other coronaviruses, such as TGEV.
National Primate Research Centers and other Primate Resources |
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Parent grant number: P51OD011104 PI: Hamm, L Lee Title of Parent Project: Tulane National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD011132 PI: Lewin, Jonathan S Title of Parent Project: Support of Yerkes National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD011092 PI: Barr-Gillespie, Peter G Title of Parent Project: Support for National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD010425 PI: Sullivan, Sean D Title of Parent Project: Washington National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD011107 PI: Mohapatra, Prasant Title of Parent Project: California National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P40OD024628 PI: Simmons, Joe H Title of Parent Project: Specific Pathogen Free Baboon Research Resource (SPFBRR) Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD011133 PI: Schlesinger, Larry S Title of Parent Project: The Southwest National Primate Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P51OD011092 PI: Barr-Gillespie, Peter G Title of Parent Project: Support for National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011133 PI: Schlesinger, Larry S Title of Parent Project: The Southwest National Primate Research Center - Overall Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011104 PI: Hamm, L Lee Title of Parent Project: Tulane National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: Mohapatra, Prasant Title of Parent Project: California National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: Lewin, Jonathan S Title of Parent Project: Support of Yerkes National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: Ackerman, Steven A. Title of Parent Project: Wisconsin National Primate Research Center Support Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: Martinez, Melween I. Title of Parent Project: Caribbean Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011106 PI: Ackerman, Steven A Title of Parent Project: Wisconsin National Primate Research Center Support Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: Prasant Mohapatra Title of Parent Project: California National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51 OD011132 PI: Lewin, Jonathan S Title of Parent Project: Support of Yerkes National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011107 PI: MOHAPATRA, PRASANT Title of Parent Project: California National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51 OD011133 PI: Schlesinger, Larry S. Title of Parent Project: The Southwest National Primate Research Center - Overall Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: P51OD011104 PI: Hamm, L Lee Title of Parent Project: Tulane National Primate Research Center Summary of the Supplement Source of Supplemental Funding: NIAID |
Parent grant number: U42OD010442 PI: Deepak Kushal Title of Parent Project: Establishment of a SPF Rhesus Macaque Colony Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD011123 PI: Charlotte Hotchkiss (CONTACT); Title of Parent Project: WaNPRC Macaca nemestrina SPF Breeding Colony Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD010990-20W1 PI: Jeffrey Roberts Title of Parent Project: Production of Pedigreed SPF Rhesus Macaques Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD011023 PI: Joyce Kimberly Cohen Title of Parent Project: "Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research Center" Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P40OD028116 PI: Diogo Magnani (contact); Kathleen Engelman Title of Parent Project: Nonhuman Primate Antibody Resource for Immune Cell Depletion Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD021324-05 PI: Betsy M Ferguson Title of Parent Project: Genomic sequencing to establish a macaque genotype and phenotype research resource Summary of the Supplement Source of Supplemental Funding: ORIP |
Mutant Mouse Research and Resources Centers and other Rodent Resources |
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Parent grant number: U42OD010924 PI: Magnuson, Terry R Title of Parent Project: A Carolina Center to Characterize and Maintain Mutant Mice Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD010921 PI: Lutz, Cathleen M (contact); Reinholdt, Laura G Title of Parent Project: The Mutant Mouse Resource and Research Center at The Jackson Laboratory Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD026440 PI: Greiner, Dale Leslie (contact); Brehm, Michael Allen; Emerson, Charles P; Luban, Jeremy ; Shultz, Leonard Title of Parent Project: Immunogenicity of Human Stem Cell-Derived Beta Cells and Muscle Cells in Humanized Mice Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P40OD011102 PI: Reinholdt, Laura G (contact); Lutz, Cathleen M Title of Parent Project: Special Mouse Strains Resource Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD012210 PI: Lloyd, KC Kent Title of Parent Project: Mutant Mouse Resource and Research Center at UC Davis Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD010918 PI: Franklin, Craig L. (contact); James Amos-Landgraf Title of Parent Project: The Mutant Mouse Resource and Research Center at the University of Missouri Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: P40OD011062 PI: Elizabeth C. Bryda Title of Parent Project: Rat Resource and Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD010924 PI: Terry R Magnuson Title of Parent Project: A Carolina Center to Characterize and Maintain Mutant Mice Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD012210 PI: KC Kent Lloyd Title of Parent Project: Mutant Mouse Resource and Research Center at UC Davis Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD010918 PI: Craig Franklin (contact); James Amos-Landgraf Title of Parent Project: The Mutant Mouse Resource and Research Center at the University of Missouri Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD024617 PI: Melinda R Dwinell Title of Parent Project: Hybrid Rat Diversity Program Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: UM1OD023222-09 PI: BRAUN, ROBERT E Title of Parent Project: The Jackson Laboratory Knockout Mouse Production and Phenotyping Project(JAX KOMP2) Summary of the Supplement Source of Supplemental Funding: Common Fund/DPCPSI |
Other ORIP Grantees |
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Parent grant number: R24OD030002 PI: Perrimon, Norbert Title of Parent Project: TRiP resources for modeling human disease Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: U42OD011140 PI: Randall Prather (contact); Kevin D. Wells Title of Parent Project: National Swine Resource and Research Center Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD022005 PI: Hugo J Bellen Title of Parent Project: A Human cDNA Library for Functional Gene Replacement in Drosophila Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD024624 PI: Gary Joseph Patti Title of Parent Project: A comprehensive resource for high-throughput profiling of worm and zebrafish metabolomes Summary of the Supplement Source of Supplemental Funding: ORIP |
Parent grant number: R24OD018559 PI: Keith Chi Cheng Title of Parent Project: Groundwork for a Synchrotron MicroCT Imaging Resource for Biology (SMIRB) Summary of the Supplement Source of Supplemental Funding: ORIP |
SARS-CoV-2 and Coronavirus-Related interactions (BioGRID)
The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein interaction data from model organisms and humans (thebiogrid.org). Visit the COVID-19 Coronavirus Project page: https://thebiogrid.org/project/3
Other Tools and Resources
NIH Literature Search Tools
- iSearch COVID-19 Portfolio: icite.od.nih.gov/covid19/search
- LitCovid: www.ncbi.nlm.nih.gov/research/coronavirus
Centers for Disease Control and Prevention (CDC)
- COVID-19 and animals: www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html
United States Department of Agriculture (USDA)
- COVID-19 for the general public: www.usda.gov/coronavirus
- Confirmed cases of SARS-CoV-2 in animals in the United States: www.aphis.usda.gov/aphis/ourfocus/animalhealth/sa_one_health/sars-cov-2-animals-us
American Veterinary Medical Association
- SARS-CoV-2 in animals, including pets: www.avma.org/resources-tools/animal-health-and-welfare/covid-19/sars-cov-2-animals-including-pets
- Testing animals for SARS-CoV-2: www.avma.org/resources-tools/animal-health-and-welfare/covid-19/testing-animals-sars-cov-2
Other Veterinary Resources
- Cornell Feline Health Center: www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/coronavirus-update
Charles River Laboratories
- COVID-19 resources for researchers: www.criver.com/products-services/support-your-covid-19-research?region=3601
- Technical information on sarbecoviruses, a subgenus of coronaviruses: www.criver.com/sites/default/files/resource-files/RM-TS-Sarbecoviruses.pdf
Other NIH Resources
Last updated: 11-08-2021