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 illustrates the host range of SARS-CoV-2 and the animals susceptible to SARS-CoV-2 infection. 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.)


Animal	Mode of Transmission	Select References
cat	respiratory tract, rectal swab, airborne	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.
ferret	respiratory tract, rectal swab, contact, airborne	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.
fruit bat	respiratory tract, contact	Abdel-Moneim AS, Abdelwhab, EM. Evidence for SARS-CoV-2 infection of animal hosts. Pathogens 2020;9(7):E529. doi: 10.3390/pathogens9070529.
hACE2 mouse	respiratory tract, fecal swab	Bao L, Deng W, Huang B, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 2020. doi: 10.1038/s41586-020-2312-y.
hamster	respiratory tract, rectal swab, contact	Sia SF, Yan L, Chin AWH, et al. Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters. Research Square. doi: 10.21203/rs.3.rs-20774/v1.
nonhuman primate	respiratory tract, contact, airborne	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.
tree shrew	respiratory tract, fecal swab	Abdel-Moneim AS, Abdelwhab, EM. Evidence for SARS-CoV-2 infection of animal hosts. Pathogens 2020;9(7):E529. doi: 10.3390/pathogens9070529.

Animal	Coronavirus	Select References
chicken	infectious bronchitis virus (IBV)	de Wit JJ, Cook JKA. Spotlight on avian coronaviruses. Avian Pathol 2020;49(4):313–316. doi: 10.1080.03079457.2020.1761010.
dog	SARS-CoV, canine coronavirus (CCoV)	Guan Y, Zheng BJ, He YQ, et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 2003;302(5643):276–278. doi: 10.1126/science.1087139. Pratelli A, Tinelli A, Decaro N, et al. Safety and efficacy of a modified-live canine coronavirus vaccine in dogs. Vet Microbiol 2004;99:43–49. doi: 10.1016/j.vetmic.2003.07.009.
duck	novel duck coronavirus	Chen G, Zhuang Q, Wang K, et al. Identification and survey of a novel avian coronavirus in ducks. PLoS One 2013;8(8):e72918. doi: 10.1371/journal.pone.0072918.
hACE2 mouse	SARS-CoV	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.
hDPP4 mouse	MERS-CoV	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. 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.
lung-only mouse	MERS-CoV	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.
pig	porcine deltacoronavirus (PDCoV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV)	Stoian A, Rowland RRR, Petrovan V, et al. The use of cells from ANPEP knockout pigs to evaluate the role of aminopeptidase N (APN) as a receptor to porcine deltacoronavirus (PDCoV) . Virology 2020;541:136–140. doi: 10.1016/j.virol.2019.12.007. Whitworth KM, Rowland RRR, Petrovan V, et al. Resistance to coronavirus infection in amino peptidase N-deficient pigs. Transgenic Res 2019;28(1):21–32. doi: 10.1007/s11248-018-0100-3. Whitworth KM, Benne JA, Spate LD, et al. Zygote injection of CRISPR/Cas9 RNA successfully modifies the target gene without delaying blastocyst development or altering the sex ratio in pigs. Transgenic Res 2017;26(1):97–107. doi: 10.1007/s11248-016-9989-6.

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.

December 1, 2023

Susceptible Animal Species and Animal Models for Coronavirus Research

Select References—Animal Models for Coronavirus Research

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