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Article

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

1
Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany
2
Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, 1455 Copenhagen, Denmark
3
Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
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Member of the German Lung Research Center (DZL), Feulgenstrasse 12, 35392 Giessen, Germany
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German Center for Infection Research, DZIF, External Partner Site, 60596 Frankfurt am Main, Germany
7
School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Markus R. Meyer
Metabolites 2021, 11(10), 699; https://doi.org/10.3390/metabo11100699
Received: 23 August 2021 / Revised: 26 September 2021 / Accepted: 6 October 2021 / Published: 13 October 2021
(This article belongs to the Section Pharmacology and Drug Metabolism)
SARS-CoV-2 is causing the coronavirus disease 2019 (COVID-19) pandemic, for which effective pharmacological therapies are needed. SARS-CoV-2 induces a shift of the host cell metabolism towards glycolysis, and the glycolysis inhibitor 2-deoxy-d-glucose (2DG), which interferes with SARS-CoV-2 infection, is under development for the treatment of COVID-19 patients. The glycolytic pathway generates intermediates that supply the non-oxidative branch of the pentose phosphate pathway (PPP). In this study, the analysis of proteomics data indicated increased transketolase (TKT) levels in SARS-CoV-2-infected cells, suggesting that a role is played by the non-oxidative PPP. In agreement, the TKT inhibitor benfooxythiamine (BOT) inhibited SARS-CoV-2 replication and increased the anti-SARS-CoV-2 activity of 2DG. In conclusion, SARS-CoV-2 infection is associated with changes in the regulation of the PPP. The TKT inhibitor BOT inhibited SARS-CoV-2 replication and increased the activity of the glycolysis inhibitor 2DG. Notably, metabolic drugs like BOT and 2DG may also interfere with COVID-19-associated immunopathology by modifying the metabolism of immune cells in addition to inhibiting SARS-CoV-2 replication. Hence, they may improve COVID-19 therapy outcomes by exerting antiviral and immunomodulatory effects. View Full-Text
Keywords: SARS-CoV-2; COVID-19; antiviral therapy; pentose phosphate pathway; oxythiamine; benfooxythiamine; 2-deoxy-d-glucose SARS-CoV-2; COVID-19; antiviral therapy; pentose phosphate pathway; oxythiamine; benfooxythiamine; 2-deoxy-d-glucose
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MDPI and ACS Style

Bojkova, D.; Costa, R.; Reus, P.; Bechtel, M.; Jaboreck, M.-C.; Olmer, R.; Martin, U.; Ciesek, S.; Michaelis, M.; Cinatl, J., Jr. Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy. Metabolites 2021, 11, 699. https://doi.org/10.3390/metabo11100699

AMA Style

Bojkova D, Costa R, Reus P, Bechtel M, Jaboreck M-C, Olmer R, Martin U, Ciesek S, Michaelis M, Cinatl J Jr. Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy. Metabolites. 2021; 11(10):699. https://doi.org/10.3390/metabo11100699

Chicago/Turabian Style

Bojkova, Denisa, Rui Costa, Philipp Reus, Marco Bechtel, Mark-Christian Jaboreck, Ruth Olmer, Ulrich Martin, Sandra Ciesek, Martin Michaelis, and Jindrich Cinatl Jr. 2021. "Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy" Metabolites 11, no. 10: 699. https://doi.org/10.3390/metabo11100699

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