Targeting the pentose phosphate pathway for sars-cov-2 therapy
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Targeting the pentose phosphate pathway for sars-cov-2 therapy. / Bojkova, Denisa; Costa, Rui; Reus, Philipp; Bechtel, Marco; Jaboreck, Mark Christian; Olmer, Ruth; Martin, Ulrich; Ciesek, Sandra; Michaelis, Martin; Cinatl, Jindrich.
I: Metabolites, Bind 11, Nr. 10, 699, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Targeting the pentose phosphate pathway for sars-cov-2 therapy
AU - Bojkova, Denisa
AU - Costa, Rui
AU - Reus, Philipp
AU - Bechtel, Marco
AU - Jaboreck, Mark Christian
AU - Olmer, Ruth
AU - Martin, Ulrich
AU - Ciesek, Sandra
AU - Michaelis, Martin
AU - Cinatl, Jindrich
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
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.
AB - 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 - 2-deoxy-D-glucose
KW - Antiviral therapy
KW - Benfooxythiamine
KW - COVID-19
KW - Oxythiamine
KW - Pentose phosphate pathway
KW - SARS-CoV-2
U2 - 10.3390/metabo11100699
DO - 10.3390/metabo11100699
M3 - Journal article
C2 - 34677415
AN - SCOPUS:85117711251
VL - 11
JO - Metabolites
JF - Metabolites
SN - 2218-1989
IS - 10
M1 - 699
ER -
ID: 285797778