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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Virus Eradication |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2055664022002436 |
| _version_ | 1811183334594707456 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Laxmikant Wali |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:45:00Z |
| format | Article |
| id | doaj.art-195f3aaeeedf494b81a101e36aaa07a3 |
| institution | Directory Open Access Journal |
| issn | 2055-6640 |
| language | English |
| last_indexed | 2024-04-11T09:45:00Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Virus Eradication |
| spelling | doaj.art-195f3aaeeedf494b81a101e36aaa07a32022-12-22T04:31:01ZengElsevierJournal of Virus Eradication2055-66402022-12-0184100305Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2Laxmikant Wali0Michael Karbiener1Scharon Chou2Vitalii Kovtunyk3Adam Adonyi4Irene Gösler5Ximena Contreras6Delyana Stoeva7Dieter Blaas8Johannes Stöckl9Thomas R. Kreil10Guido A. Gualdoni11Anna-Dorothea Gorki12G.ST Antivirals GmbH, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, AustriaG.ST Antivirals GmbH, AustriaG.ST Antivirals GmbH, AustriaG.ST Antivirals GmbH, AustriaCenter of Medical Biochemistry, Max Perutz Labs, Vienna Biocenter, Medical University of Vienna, AustriaG.ST Antivirals GmbH, AustriaG.ST Antivirals GmbH, AustriaCenter of Medical Biochemistry, Max Perutz Labs, Vienna Biocenter, Medical University of Vienna, AustriaInstitute of Immunology, Center of Pathophysiology, Immunology & Infectiology, Medical University of Vienna, AustriaGlobal Pathogen Safety, Takeda Manufacturing Austria AG, AustriaG.ST Antivirals GmbH, AustriaG.ST Antivirals GmbH, Austria; Corresponding author. G.ST Antivirals GmbH, Doktor-Bohr-Gasse 7 (VBC6), 1030, Vienna, Austria.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.http://www.sciencedirect.com/science/article/pii/S2055664022002436AntiviralBroad-spectrum antiviral therapy2-DGRhinovirusCoronavirusSARS-CoV-2 |
| spellingShingle | 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 Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 Journal of Virus Eradication Antiviral Broad-spectrum antiviral therapy 2-DG Rhinovirus Coronavirus SARS-CoV-2 |
| title | Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 |
| title_full | Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 |
| title_fullStr | Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 |
| title_full_unstemmed | Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 |
| title_short | Host-directed therapy with 2-deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2 |
| title_sort | host directed therapy with 2 deoxy d glucose inhibits human rhinoviruses endemic coronaviruses and sars cov 2 |
| topic | Antiviral Broad-spectrum antiviral therapy 2-DG Rhinovirus Coronavirus SARS-CoV-2 |
| url | http://www.sciencedirect.com/science/article/pii/S2055664022002436 |
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