TY  - JOUR
A1  - Bojkova, Denisa
A1  - Costa, Rui
A1  - Reus, Philipp
A1  - Bechtel, Marco
A1  - Jaboreck, Mark-Christian
A1  - Olmer, Ruth Maria
A1  - Martin, Ulrich
A1  - Ciesek, Sandra
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - Targeting the pentose phosphate pathway for SARS-CoV-2 therapy
T2  - Metabolites
N2  - 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.
KW  - SARS-CoV-2
KW  - COVID-19
KW  - antiviral therapy
KW  - pentose phosphate pathway
KW  - oxythiamine
KW  - benfooxythiamine
KW  - 2-deoxy-d-glucose
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74209
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-742098
SN  - 2218-1989
VL  - 11.2021
IS  - 10, 699
PB  - MDPI
CY  - Basel
ER  -