| Autor: |
Bojkova D; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany., Costa R; Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, 1455 Copenhagen, Denmark., Reus P; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany., Bechtel M; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany., Jaboreck MC; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.; Member of the German Lung Research Center (DZL), Feulgenstrasse 12, 35392 Giessen, Germany., Olmer R; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.; Member of the German Lung Research Center (DZL), Feulgenstrasse 12, 35392 Giessen, Germany., Martin U; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.; Member of the German Lung Research Center (DZL), Feulgenstrasse 12, 35392 Giessen, Germany., Ciesek S; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.; German Center for Infection Research, DZIF, External Partner Site, 60596 Frankfurt am Main, Germany., Michaelis M; School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK., Cinatl J Jr; Institute for Medical Virology, University Hospital, Goethe University, 60596 Frankfurt am Main, Germany. |
| Abstrakt: |
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. |
