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Review
. 2022 Sep 12;27(18):5928.
doi: 10.3390/molecules27185928.

The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses

Beata Pająk  1   2 , Rafał Zieliński  3 , John Tyler Manning  4 , Stanislava Matejin  5 , Slobodan Paessler  4 , Izabela Fokt  3 , Mark R Emmett  4 , Waldemar Priebe  3
Affiliations
Review

The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses

Beata Pająk et al. Molecules. .

Abstract

Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is a common mechanism of cell adaptation to several viral infections, including noroviruses, rhinoviruses, influenza virus, Zika virus, cytomegalovirus, coronaviruses and others. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Glycolysis inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied as antiviral agents. However, 2-DG's poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss the potential of 2-DG and its novel analogs as potent promising antiviral drugs with special emphasis on targeted intracellular processes.

Keywords: 2-deoxy-D-glucose; SARS-CoV-2; glycolysis; glycosylation; metabolic shift; novel analogs; viral infections.

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Conflict of interest statement

Moleculin Inc. partially finances research concerning molecular mechanisms of 2-DG analogs, including WP1122 action. W.P. is an inventor of patents covering new derivatives of 2-DG. He is the chair of SAB and a shareholder of Moleculin Biotech. Inc., CNS Pharmaceuticals, and WPD Pharmaceuticals. His research is in part supported by a sponsor research grant from Moleculin Biotech. Inc. and CNS Pharmaceuticals. M.E. is a shareholder of Moleculin Biotech. Inc., and his research is in part supported by a sponsor research grant from Moleculin Biotech. Inc. I.F. and R.Z. are listed as inventors on patents covering new analogs of 2-DG and are consultants of Moleculin Biotech., Inc., and are shareholders of Moleculin Biotech, Inc. and CNS Pharmaceuticals. B.P. is the CSO at WPD Pharmaceuticals. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
2-Deoxy-D-glucose (2-DG) and its biological effects. (A). Structures of D-Glucose, D-Mannose and 2-DG; (B). The effects of 2-DG on the glycolysis pathway and substitution for mannose in N-glycan synthesis; (C). Truncation of N-glycosylation by 2-DG.
Figure 2
Figure 2
Structures of D-mannose, D-glucose, 2-DG (2-deoxy-D-glucose; 2-deoxy-D-mannose), and WP1122 (2-DG prodrug). Within the cell, WP1122 is deacetylated by cellular esterases to monoacetates: WP1124 and WP1125, and subsequently release active 2-DG.
Figure 3
Figure 3
Structures of (A). 2-deoxy-2-fluoro-D-glucose (2-FG), (B). 2-deoxy-2-chloro-D-glucose (2-CG), and (C). 2-deoxy-2-bromo-D-glucose (2-BG).
See this image and copyright information in PMC

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