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

Bojkova, Denisa, Costa, Rui, Reus, Philipp, Bechtel, Marco, Jaboreck, Mark-Christian, Olmer, Ruth, Martin, Ulrich, Ciesek, Sandra, Michaelis, Martin, Cinatl, Jindrich and others. (2021) Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy. Metabolites, 11 (10). Article Number 699. E-ISSN 2218-1989. (doi:10.3390/metabo11100699) (KAR id:91274)

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Official URL:
https://doi.org/10.3390/metabo11100699

Abstract

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.

Item Type: Article
DOI/Identification number: 10.3390/metabo11100699
Uncontrolled keywords: SARS-CoV-2; COVID-19; antiviral therapy; pentose phosphate pathway; oxythiamine; benfooxythiamine; 2-deoxy-d-glucose
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 02 Nov 2021 16:11 UTC
Last Modified: 14 Nov 2022 23:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91274 (The current URI for this page, for reference purposes)
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
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