Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2

Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways such as glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-d-glucose (2-DG), we assessed the dose-dependent inhibition of viral replication of minor- and ma...

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Bibliographic Details
Main Authors: Laxmikant Wali, Michael Karbiener, Scharon Chou, Vitalii Kovtunyk, Adam Adonyi, Irene Gösler, Ximena Contreras, Delyana Stoeva, Dieter Blaas, Johannes Stöckl, Thomas R. Kreil, Guido A. Gualdoni, Anna-Dorothea Gorki
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Journal of Virus Eradication
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Online Access:http://www.sciencedirect.com/science/article/pii/S2055664022002436
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Summary:Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways such as glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-d-glucose (2-DG), we assessed the dose-dependent inhibition of viral replication of minor- and major-receptor group RVs in epithelial cells. 2-DG disrupted RV infection cycle by inhibiting template negative-strand as well as genomic positive-strand RNA synthesis, resulting in less progeny virus and RV-mediated cell death. Assessment of 2-DG's intracellular kinetics revealed that after a short-exposure to 2-DG, the active intermediate, 2-DG6P, is stored intracellularly for several hours. Finally, we confirmed the antiviral effect of 2-DG on pandemic SARS-CoV-2 and showed for the first time that it also reduces replication of endemic human coronaviruses. These results provide further evidence that 2-DG could be used as a broad-spectrum antiviral.
ISSN:2055-6640