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 and other Primate Resources

 
National Primate Research Centers and other Primate Resources

Parent grant number: P51OD011106

PI: Ackerman, Steven A

Title of Parent Project: Wisconsin National Primate Research Center Support
Title of Administrative Supplement: Wisconsin National Primate Research Center Support

Summary of the Supplement
The Wisconsin National Primate Center at the University of Wisconsin-Madison will renovate quarantine suites into ABSL3-space though purchase and installation of two ready-to-use biobubble containment enclosures as well as associated equipment (i.e., imaging, molecular biology, diagnostic, necropsy, etc.) to support SARS-CoV-2 challenge studies.

Source of Supplemental Funding: NIAID
 

Parent grant number: P51OD011107

PI: Prasant Mohapatra

Title of Parent Project: California National Primate Research Center
Title of Administrative Supplement: California National Primate Research Center

Summary of the Supplement
The California National Primate Research Center at the University of California at Davis will conduct an Operation Warp Speed therapeutic study designed to understand what neutralizing antibody titer is needed to ameliorate disease in an early postexposure SARS-CoV-2 nonhuman primate model, which represents people who have mild disease/outpatients. This information is needed to inform therapeutic human clinical trials that are currently being planned and will lay the foundation for future studies for testing efficacy later in infection, representing patients who are hospitalized with severe disease.

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
Title of Administrative Supplement: Support of Yerkes National Primate Research Center

Summary of the Supplement
The Yerkes National Primate Research Center at Emory University will conduct multiple facility and equipment enhancements in support of COVID-19 research in the ABSL-3 and BSL-3 facilities. The proposed equipment for purchase and use will provide optimal support for a large base of NIH-funded COVID-19 research projects at the Yerkes NPRC, ultimately contributing to the development of safe and effective vaccines and therapeutics for COVID-19.

Source of Supplemental Funding: NIAID
 

Parent grant number: P51OD011107

PI: MOHAPATRA, PRASANT

Title of Parent Project: California National Primate Research Center
Title of Administrative Supplement: California National Primate Research Center

Summary of the Supplement
The California National Primate Research Center at the University of California at Davis will purchase steel overhead structures for two half-acre field corrals which will support increased breeding to ensure a continued pipeline of rhesus macaques for COVID-19 research as well as equipment for an ABSL-3 suite to support infectious disease research on SARS-CoV-2.

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
Title of Administrative Supplement: Significant expansion of the SNPRC ABSL3 capability in the wake of COVID-19

Summary of the Supplement
The Southwest National Primate Research Center at the Texas Biomedical Research Institute will renovate and equip a recently decommissioned ABSL3 facility, thus increasing ABSL3 capacity for COVID-19 research.

Source of Supplemental Funding: NIAID
 

Parent grant number: P51OD011104

PI: Hamm, L Lee

Title of Parent Project: Tulane National Primate Research Center
Title of Administrative Supplement: Improving Research Resources at the TNPRC to Support COVID-19 Research

Summary of the Supplement
The Tulane National Primate Research Center at the Tulane University will enrich research resources for COVID-19 research through two specific resource improvements: expansion of specific pathogen free (SPF) rhesus macaque breeding colony housing infrastructure and the purchase of high-end laboratory instrumentation for BSL-2/3 laboratory space to support COVID-19 studies.

Source of Supplemental Funding: NIAID
 

Parent grant number: U42OD010442

PI: Deepak Kushal

Title of Parent Project: Establishment of a SPF Rhesus Macaque Colony
Title of Administrative Supplement: PCR and antibody screening for SARS-CoV-2 in the SNPRC rhesus macaque colony

Summary of the Supplement
The purpose of this administrative supplement is to screen the entire SNPRC U42 rhesus macaque colony for both SARS-CoV-2 virus and antibodies using established approaches and to develop faster and less expensive in-house tests for SARS-CoV-2. The methods and results of this work at SNPRC will be disseminated to other primate centers maintaining SPF macaque breeding colonies. The Center will implement and develop methods for SARS-CoV-2 surveillance in the SNPRC SPF rhesus macaque breeding colony, allowing the detection and mitigation of a SARS-CoV-2 outbreak in the colony.

Source of Supplemental Funding: ORIP
 

Parent grant number: U42OD011123

PI: Charlotte Hotchkiss (CONTACT);
Sally Thompson-Iritani

Title of Parent Project: WaNPRC Macaca nemestrina SPF Breeding Colony
Title of Administrative Supplement: Development of a COVID-19 Testing Program for SPF M. nemestrina

Summary of the Supplement
The purpose of this administrative supplement is to ensure that the current COVID-19 pandemic does not negatively affect the health of pigtail macaques within the SPF breeding colony, affect the health of individuals who work with these animals, or interfere with the usefulness of pigtail macaques as models for HIV/AIDS research or for COVID-19 research with surplus animals. The Center will develop and validate virus and antibody tests for macaque coronaviruses, including SARS-CoV-2 and seasonal coronaviruses in pigtail macaques; determine the most efficient and accurate sampling and testing methods; and screen animals within the SPF pigtail macaque colony . The methods and results of this work at WaNPRC will be disseminated to other primate centers maintaining SPF macaque breeding colonies.

Source of Supplemental Funding: ORIP
 

Parent grant number: U42OD010990-20W1

PI: Jeffrey Roberts

Title of Parent Project: Production of Pedigreed SPF Rhesus Macaques
Title of Administrative Supplement: California National Primate Research Center

Summary of the Supplement
The purpose of this administrative supplement is to expand the viral agents excluded for level 1 and 2 SPF macaque colonies to include SARS-CoV-2 as SPF NHP macaque populations are at risk for COVID-19. The Center will implement and develop methods for SARS-CoV-2 surveillance in the CNPRC SPF rhesus macaque breeding colony, allowing the detection and mitigation of a SARS-CoV-2 outbreak in the colony. The methods and results of the work will be disseminated to other primate centers maintaining SPF macaque breeding colonies through the NPRC Pathogen Detection Working Group and via ongoing interactions with ORIP program staff.

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"
Title of Administrative Supplement: "Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research Center"

Summary of the Supplement
"The purpose of this administrative supplement is to add screening for evidence of SARS-CoV-2 infection by developing and implementing molecular and serologic methods for detecting SARS-CoV-2 infection and immunity in the SPF rhesus macaque colony at the Yerkes NPRC. The proposal will also add genetic screening which will define and determine the frequency of distinct ACE2 coding alleles within the colony. The methods and results of this work at Yerkes will be disseminated to other primate centers housing SPF macaque colonies."

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
Title of Administrative Supplement: Nonhuman Primate Antibody Resource for Immune Cell Depletion

Summary of the Supplement
"The purpose of this administrative supplement is to create safe recombinant reference macaque immunoglobulin standards to facilitate the development and validation of reliable assays for the detection of pathogenic coronaviruses and antiviral antibodies in nonhuman primate (NHP) animal models of COVID. Specifically, this supplement will fund the generation of the following reagents: recombinant coronavirus-reactive rhesus monoclonal IgGs and NHP serum reference standards. These macaque reference antibody reagents will improve the performance and comparability of antibody-based assays for NHP models by facilitating serum assay development, proficiency training, and inter-laboratory performance comparisons at NHP centers and laboratories.

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
Title of Administrative Supplement: Genomic and Immunogenetic Resource to Support SRA-CoV-2/COVID-19 Nonhuman Primate Research

Summary of the Supplement
"The purpose of this administrative supplement is to extend a centralized resource (mGAP) to include the generation, analysis and dissemination of genomic sequence variants from nonhuman primates used in SARS-CoV-2 studies (the new SARS-CoV-2 portal will be located within the mGAP website). The proposed work, in conjunction with the mGAP resource, will support studies to understand how host genetic variation influences vaccine and treatment efficacy."

Source of Supplemental Funding: ORIP
Mutant Mouse Research and Resources Centers and other Rodent Resources

 
Mutant Mouse Research and Resources Centers and other Rodent Resources

Parent grant number: P40OD011062

PI: Elizabeth C. Bryda

Title of Parent Project: Rat Resource and Research Center
Title of Administrative Supplement: Generation of Novel Rat Models for the Study of SARS-CoV-2 and COVID-19

Summary of the Supplement
The Center will generate novel hACE2-expressing rat models for the study of pathogenesis and evaluation of vaccines and antiviral therapies for viruses like SARS-CoV-2 that use hACE2 for entry into host cells. Humanized rats will be generated by random integration and targeted knock-in of human ACE2 in both inbred (F344) and outbred (SD) genetic backgrounds. These animals after preliminary characterization will be readily available to the broad scientific community.

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
Title of Administrative Supplement: A Carolina Center to Characterize and Maintain Mutant Mice

Summary of the Supplement
"The Center will archive and distribute several existing SARSCoV2 mouse models, accelerating the availability of these mouse strains; supporting the development and phenotypic analysis of the new strains to address limitations of the existing transgenic models for more rigorous study of infection and disease. The resources generated by the supplement will meet the urgent need of the biomedical community for expanded access to current SARSCoV2 mouse models and the creation of newer improved models to inform preclinical development and testing of vaccines and therapeutics."

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
Title of Administrative Supplement: Production, validation, and distribution of humanized COVID-19 relevant mouse models

Summary of the Supplement
The Center will generate urgently needed mouse models for SARS-CoV-2 and COVID-19 biomedical research. These models will utilize variety of human gene products affecting SARC-CoV2 entrance into the cells, as well as other human gene products that play key roles in the host inflammatory and immune response to disease, and are potentially involved in the severity of COVID-19 in patients with co-morbidities, such as diabetes. Therefore, this proposal will breed, validate, and distribute new knockin/knockout models of pathogenic coronaviruses including SARS-CoV-2 suitable for studying the pathogenesis of these viruses and screening vaccines and therapeutics.

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
Title of Administrative Supplement: Optimization of murine models of COVID-19 through gut microbiota manipulation

Summary of the Supplement
The purpose of this administrative supplement is to refine and optimize mouse models for the study of SARS-CoV-2 infection (COVID-19). The proposed project will assess how increasing antigen exposure of mice through supplementation of standardized complex gut microbiotas with selected viral and bacterial agents will modulate the phenotype of this model. Results generated will be invaluable and immediately applicable to ongoing studies of the devastating COVID-19 pandemic and mice developed will be immediately available to the biomedical research community.

Source of Supplemental Funding: ORIP
 

Parent grant number: R24OD024617

PI: Melinda R Dwinell

Title of Parent Project: Hybrid Rat Diversity Program
Title of Administrative Supplement: Hybrid Rat Diversity Program - humanized hACE2rat resource for COVID research

Summary of the Supplement
"The purpose of this administrative supplement is to develop a resource of engineered ACE2 humanized rat models, a key receptor for multiple human coronaviruses including SARS-CoV and SARS-CoV-2, to meet the pressing challenges faced by COVID-19 and future similar outbreaks. The development of engineered ACE2 humanized rat models on two genetic backgrounds will enable clinical translation needed for treatment and prevention of human coronaviruses including SARSCoV-2."

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)
Title of Administrative Supplement: The Jackson Laboratory Knockout Mouse Production and Phenotyping Project(JAX KOMP2)

Summary of the Supplement
"The Jackson Laboratory will develop the next generation of precision mouse models for mechanistic discovery of SARS-CoV2 infection and therapeutic discovery of COVID-19 disease treatments. This new mouse model platform will incorporate diverse genetic backgrounds, to characterize the variation in SARS-CoV-2 infection dynamics and the development of clinically-relevant disease. The project will rapidly provide the research community with an urgently needed resource for linking the variability in COVID-19 disease outcome with underlying host genetic features, and for developing precision therapies tailored to treat the individual patient."

Source of Supplemental Funding: Common Fund/DPCPSI
Other ORIP Grantees

 
Other ORIP Grantees

Parent grant number: U42OD011140

PI: Randall Prather (contact); Kevin D. Wells

Title of Parent Project: National Swine Resource and Research Center
Title of Administrative Supplement: Swine Resource and Research Center COVID Administrative Supplement

Summary of the Supplement
The Center will generate a large animal model (pig) that recapitulates human symptoms associated with SARS viruses that use angiotensin converting enzyme 2 (ACE2) as an entry receptor. This project will produce pigs that harbor a fully functional, human ACE2. The immediate application of this large animal model is related to near-term testing of devices, strategies, and therapies in the context of translational medicine. In the long term, this model will be used to further the understanding of SARS biology and the host response.

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
Title of Administrative Supplement: A Comprehensive Human cDNA Library for Functional Gene Replacement in Drosophila

Summary of the Supplement
"The purpose of this administrative supplement is to generate a comprehensive library of transgenic and mutant Drosophila for studies of COVID-19. The proposed project will allow investigators to study the 26 protein coding genes for SARS-CoV-2 by expressing them in Drosophila to assess the consequences of their expression. This proposal will also create tools to study over 300 human genes that have been shown to bind to viral proteins that may be involved in COVID-19."

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
Title of Administrative Supplement: A comprehensive resource for high-throughput profiling of worm and zebrafish metabolomes

Summary of the Supplement
"The purpose of this project is to develop a resource that will enable researchers to use model organisms to rapidly screen drug targets and potential disease mechanisms. This project will facilitate the application of metabolomics to COVID-19 related studies in worms and zebrafish. The metabolic dysfunction uncovered in human patients will be mapped to the worm and zebrafish metabolomes by using technologies developed in the parent award. Comparing metabolic changes from each of these models to reference COVID-19 pathways will improve understanding of which disease processes contribute to COVID-19 pathology."

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)
Title of Administrative Supplement: Groundwork for a Synchrotron MicroCT Imaging Resource for Biology (SMIRB)

Summary of the Supplement
The purpose of this administrative supplement is to support an equipment upgrade (Micro-CT), thus improving resolution when producing a 3D form of histology (X-ray histotomography) of lung tissues from a humanized mouse model of COVID and human autopsy samples. This technology, developed in the parent R24 grant, will help to characterize the cellular and tissue geometries of COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) pneumonia (COVID-19 pandemic’s most common cause of death).

Source of Supplemental Funding: ORIP
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