Alternatives to animal models and their application in the discovery of species susceptibility to SARS-CoV-2 and other respiratory infectious pathogens: A review

The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mi...

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Veröffentlicht in:Veterinary Pathology 2022-07, Vol.59 (4), p.565-577
Hauptverfasser: Runft, Sandra, Färber, Iris, Krüger, Johannes, Krüger, Nadine, Armando, Federico, Rocha, Cheila, Pöhlmann, Stefan, Burigk, Laura, Leitzen, Eva, Ciurkiewicz, Malgorzata, Braun, Armin, Schneider, Daniel, Baumgärtner, Lars, Freisleben, Bernd, Baumgärtner, Wolfgang
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container_end_page 577
container_issue 4
container_start_page 565
container_title Veterinary Pathology
container_volume 59
creator Runft, Sandra
Färber, Iris
Krüger, Johannes
Krüger, Nadine
Armando, Federico
Rocha, Cheila
Pöhlmann, Stefan
Burigk, Laura
Leitzen, Eva
Ciurkiewicz, Malgorzata
Braun, Armin
Schneider, Daniel
Baumgärtner, Lars
Freisleben, Bernd
Baumgärtner, Wolfgang
description The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mice, rhesus macaques, ferrets, and Syrian golden hamsters have been frequently used in studies of pathogenesis and efficacy of antiviral compounds and vaccines. However, alternatives to in vivo experiments, such as immortalized cell lines, primary respiratory epithelial cells cultured at an air–liquid interface, stem/progenitor cell-derived organoids, or tissue explants, have also been used for isolation of SARS-CoV-2, investigation of cytopathic effects, and pathogen–host interactions. Moreover, initial proof-of-concept studies for testing therapeutic agents can be performed with these tools, showing that animal-sparing cell culture methods could significantly reduce the need for animal models in the future, following the 3R principles of replace, reduce, and refine. So far, only few studies using animal-derived primary cells or tissues have been conducted in SARS-CoV-2 research, although natural infection has been shown to occur in several animal species. Therefore, the need for in-depth investigations on possible interspecies transmission routes and differences in susceptibility to SARS-CoV-2 is urgent. This review gives an overview of studies employing alternative culture systems like primary cell cultures, tissue explants, or organoids for investigations of the pathophysiology and reverse zoonotic potential of SARS-CoV-2 in animals. In addition, future possibilities of SARS-CoV-2 research in animals, including previously neglected methods like the use of precision-cut lung slices, will be outlined.
doi_str_mv 10.1177/03009858211073678
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identifier ISSN: 0300-9858
ispartof Veterinary Pathology, 2022-07, Vol.59 (4), p.565-577
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subjects animal pathology
Animals
Antiviral Agents - therapeutic use
cell culture
COVID-19 - veterinary
COVID-19 infection
Cricetinae
Disease Models, Animal
disease transmission
epithelium
Ferrets
host range
liquid-air interface
Lung - pathology
lungs
Macaca mulatta
Mice
organoids
pathogenesis
pathophysiology
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
therapeutics
zoonoses
title Alternatives to animal models and their application in the discovery of species susceptibility to SARS-CoV-2 and other respiratory infectious pathogens: A review
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