AI Article Synopsis
- SARS-CoV-2, responsible for COVID-19, alters host cell metabolism to favor glycolysis, prompting research into therapies like the glycolysis inhibitor 2-deoxy-d-glucose (2DG).
- Proteomic analysis showed increased levels of transketolase (TKT) in infected cells, indicating the non-oxidative pathway of the pentose phosphate pathway may play a role in viral replication.
- The TKT inhibitor benfooxythiamine (BOT) not only restricted SARS-CoV-2 replication but also enhanced the effectiveness of 2DG, suggesting that metabolic drugs could improve COVID-19 treatments by combining antiviral and immune-modulating effects.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540749 | PMC |
| http://dx.doi.org/10.3390/metabo11100699 | DOI Listing |
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