Targeting the pentose phosphate pathway for SARS-CoV-2 therapy

  • 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.

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Author:Denisa BojkovaORCiDGND, Rui CostaORCiDGND, Philipp ReusORCiD, Marco Bechtel, Mark-Christian JaboreckORCiD, Ruth Maria OlmerGND, Ulrich MartinORCiDGND, Sandra CiesekORCiDGND, Martin MichaelisORCiDGND, Jindrich CinatlORCiDGND
URN:urn:nbn:de:hebis:30:3-742098
DOI:https://doi.org/10.3390/metabo11100699
ISSN:2218-1989
Parent Title (English):Metabolites
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2021/10/13
Date of first Publication:2021/10/13
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/06/06
Tag:2-deoxy-d-glucose; COVID-19; SARS-CoV-2; antiviral therapy; benfooxythiamine; oxythiamine; pentose phosphate pathway
Volume:11.2021
Issue:10, 699
Page Number:11
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0