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

Pająk, Beata; Zieliński, Rafał; Manning, John T.; Matejin, Stanislava; Paessler, Slobodan; Fokt, Izabela; Emmett, Mark R.; Priebe, Waldemar

doi:10.3390/molecules27185928

Cited by 22 publications

(15 citation statements)

References 87 publications

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“…, and is currently being used to treat SARS-CoV-2 [9,11,12]. Although 2DG therapy has shown promise in treating these conditions, there is lingering concerns regarding its safety.…”

Section: Discussionmentioning

confidence: 99%

“…) is a glucose analog that has garnered considerable interest in recent years as a potential therapeutic agent for various diseases characterized by abnormal glycolysis, including cancer [1][2][3][4][5], epilepsy [6], systemic lupus erythematosus (SLE) [7], rheumatoid arthritis (RA) [8], and COVID-19 [9][10][11][12]. 2DG is taken up into cells by glucose transporters and is converted by hexokinase into 2DG-6-phosphate which cannot be further broken down to yield energy, resulting in a reduction in the rate of glycolysis [13].…”

Section: -Deoxy-d-glucose (2dgmentioning

confidence: 99%

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Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

Wells

Wilson

Sears

et al. 2023

Preprint

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Objective: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear. Methods: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment. Results: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways. Conclusions: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.

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“…, and is currently being used to treat SARS-CoV-2 [9,11,12]. Although 2DG therapy has shown promise in treating these conditions, there is lingering concerns regarding its safety.…”

Section: Discussionmentioning

confidence: 99%

Section: -Deoxy-d-glucose (2dgmentioning

confidence: 99%

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

Wells

Wilson

Sears

et al. 2023

Preprint

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“…However, some studies [87, 88] and its poor pharmacokinetic properties, e.g., its short plasma half-life [89], suggest that 2-DG itself may never become a licensed drug. Nevertheless, it is a useful tool to examine the principles of glycolytic interference and novel 2-DG analogs or other glycolytic inhibitors possibly boast a better pharmacological suitability [90]. Since dependence on the host metabolism is a universal feature of all viruses, differential and strictly determined metabolic treatments may be able to alleviate all types of virus infections in the future.…”

Section: Discussionmentioning

confidence: 99%

Glycolytic interference blocks influenza A virus propagation by impairing viral polymerase-driven synthesis of genomic vRNA

Kleinehr

Daniel

Günl

et al. 2022

Preprint

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Influenza A virus (IAV), like any other virus, provokes considerable modifications of its host cell's metabolism. This includes a substantial increase in the uptake as well as the metabolization of glucose. Although it is known for quite some time that suppression of glucose metabolism restricts virus replication, the exact molecular impact on the viral life cycle remained enigmatic so far. Using 2-deoxy-D-glucose (2-DG) we examined how well inhibition of glycolysis is tolerated by host cells and which step of the IAV life cycle is affected. We observed that effects induced by 2-DG are reversible and that cells can cope with relatively high concentrations of the inhibitor by compensating the loss of glycolytic activity by upregulating other metabolic pathways. Moreover, mass spectrometry data provided information on various metabolic modifications induced by either the virus or agents interfering with glycolysis. In the presence of 2-DG viral titers were significantly reduced in a dose-dependent manner. The supplementation of direct or indirect glycolysis metabolites led to a partial or almost complete reversion of the inhibitory effect of 2-DG on viral growth and demonstrated that indeed the inhibition of glycolysis and not of N-linked glycosylation was responsible for the observed phenotype. Importantly, we could show via conventional and strand-specific qPCR that the treatment with 2-DG led to a prolonged phase of viral mRNA synthesis while the accumulation of genomic vRNA was strongly reduced. At the same time, minigenome assays showed no signs of a general reduction of replicative capacity of the viral polymerase. Therefore, our data suggest that the significant reduction in IAV replication by glycolytic interference occurs mainly due to an impairment of the dynamic regulation of the viral polymerase which conveys the transition of the enzyme's function from transcription to replication.

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“…Selected recent methodologies have been discussed here. As D-glucose and D-mannose are epimers in C-2, deoxygenation in C-2 gives an identical product, i.e., 2-DG (Figure 4) [145].…”

Section: Synthetic Methodsmentioning

confidence: 99%

2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities

Singh¹,

Gupta

Kumar

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present review, various pharmaceutical properties of 2-DG are discussed.

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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

Cited by 22 publications

References 87 publications

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice

Glycolytic interference blocks influenza A virus propagation by impairing viral polymerase-driven synthesis of genomic vRNA

2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities

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