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Article

Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

1
Land & Water, Commonwealth Scientific and Industrial Research Organisation, Dutton Park, QLD 4102, Australia
2
Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, VIC 3122, Australia
3
Australian Centre for Disease Preparedness (ACDP), Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC 3220, Australia
4
Department of Health Sciences, University of York, York YO10 5DD, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Meikle
Metabolites 2021, 11(5), 327; https://doi.org/10.3390/metabo11050327
Received: 30 March 2021 / Revised: 6 May 2021 / Accepted: 15 May 2021 / Published: 19 May 2021
Coronavirus disease (COVID-19) is a contagious respiratory disease that is causing significant global morbidity and mortality. Understanding the impact of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the host metabolism is still in its infancy but of great importance. Herein, we investigated the metabolic response during viral shedding and post-shedding in an asymptomatic SARS-CoV-2 ferret model (n = 6) challenged with two SARS-CoV-2 isolates. Virological and metabolic analyses were performed on (minimally invasive) collected oral swabs, rectal swabs, and nasal washes. Fragments of SARS-CoV-2 RNA were only found in the nasal wash samples in four of the six ferrets, and in the samples collected 3 to 9 days post-infection (referred to as viral shedding). Central carbon metabolism metabolites were analyzed during viral shedding and post-shedding periods using a dynamic Multiple Reaction Monitoring (dMRM) database and method. Subsequent untargeted metabolomics and lipidomics of the same samples were performed using a Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) methodology, building upon the identified differentiated central carbon metabolism metabolites. Multivariate analysis of the acquired data identified 29 significant metabolites and three lipids that were subjected to pathway enrichment and impact analysis. The presence of viral shedding coincided with the challenge dose administered and significant changes in the citric acid cycle, purine metabolism, and pentose phosphate pathways, amongst others, in the host nasal wash samples. An elevated immune response in the host was also observed between the two isolates studied. These results support other metabolomic-based findings in clinical observational studies and indicate the utility of metabolomics applied to ferrets for further COVID-19 research that advances early diagnosis of asymptomatic and mild clinical COVID-19 infections, in addition to assessing the effectiveness of new or repurposed drug therapies. View Full-Text
Keywords: animal model; COVID-19; ferret; lipidomics; metabolomics; SARS-CoV-2; systems biology animal model; COVID-19; ferret; lipidomics; metabolomics; SARS-CoV-2; systems biology
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MDPI and ACS Style

Beale, D.J.; Shah, R.; Karpe, A.V.; Hillyer, K.E.; McAuley, A.J.; Au, G.G.; Marsh, G.A.; Vasan, S.S. Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection. Metabolites 2021, 11, 327. https://doi.org/10.3390/metabo11050327

AMA Style

Beale DJ, Shah R, Karpe AV, Hillyer KE, McAuley AJ, Au GG, Marsh GA, Vasan SS. Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection. Metabolites. 2021; 11(5):327. https://doi.org/10.3390/metabo11050327

Chicago/Turabian Style

Beale, David J., Rohan Shah, Avinash V. Karpe, Katie E. Hillyer, Alexander J. McAuley, Gough G. Au, Glenn A. Marsh, and Seshadri S. Vasan. 2021. "Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection" Metabolites 11, no. 5: 327. https://doi.org/10.3390/metabo11050327

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