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

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

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

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.

National Primate Research Centers (NPRCs) supported by ORIP

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:

Other ORIP supported nonhuman primate resources

For general information on ORIP’s nonhuman primate resources, see ORIP’s Nonhuman Primate Resources fact sheet.

 Select References—Nonhuman Primates

European Animal Research Association (EARA)

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.

Mutant Mouse Research and Resource Centers (MMRRC)

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.

Other ORIP supported rodent resources ORIP

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

Mouse Genome Informatics Coronavirus Information Center

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.

Other Animal Models for Coronavirus Research

Chicken

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.

Pig

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.

Updates and Current Research from ORIP Grantees

National Primate Research Centers (Coming Soon)

Mutant Mouse Research and Resource Centers (Coming Soon)

Other ORIP Grantees (Coming Soon)

BioGRID Data Repository

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

Centers for Disease Control and Prevention (CDC)

United States Department of Agriculture (USDA)

American Veterinary Medical Association

Other Veterinary Resources

Charles River Laboratories

Other NIH Resources