2. Academic Validation
  3. Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

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

  • Metabolites. 2021 Oct 13;11(10):699. doi: 10.3390/metabo11100699.
Denisa Bojkova 1,  Rui Costa 2,  Philipp Reus 1 3,  Marco Bechtel 1,  Mark-Christian Jaboreck 4 5,  Ruth Olmer 4 5,  Ulrich Martin 4 5,  Sandra Ciesek 1 3 6,  Martin Michaelis 7,  Jindrich Cinatl Jr 1
Affiliations

Affiliations

  • 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.
  • 4 Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • 5 Member of the German Lung Research Center (DZL), Feulgenstrasse 12, 35392 Giessen, Germany.
  • 6 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.
PMID: 34677415 DOI: 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.

Keywords

2-deoxy-d-glucose; COVID-19; SARS-CoV-2; antiviral therapy; benfooxythiamine; oxythiamine; pentose phosphate pathway.

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