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
Published in:	Journal of Virus Eradication Vol. 8; no. 4; p. 100305
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:	Journal Article
Language:	English
Published:	Elsevier 01-12-2022
Subjects:	2-DG Antiviral Broad-spectrum antiviral therapy Coronavirus Rhinovirus SARS-CoV-2
Online Access:	Get full text
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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
DOI:	10.1016/j.jve.2022.100305