Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational

Mansouri, Kamran; Rastegari-Pouyani, Mohsen; Ghanbri-Movahed, Maryam; Safarzadeh, Mehrnoush; Kiani, Sarah; Ghanbari-Movahed, Zahra

doi:10.1016/j.biopha.2020.110694

Cited by 17 publications

(26 citation statements)

References 227 publications

(234 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 127 In COVID-19, lipogenesis (process of synthesis of fatty acids and triglycerides) is needed for virus packaging. 128 , 129 Hence, any intervention in glycolytic pathway of host will downregulate lipogenesis leading to an inhibition in pyruvate production and will eventually prevent it from entering into TCA cycle. 129 Various glycolytic inhibitors that are designed against AMPK (AMP-activated protein kinase, the ultimate energy-sensor in eukaryotic cells which shut down ATP-consuming processes) are metformine, lipoic acid, resveratrol, ivermectin and so on.…”

Section: Host Pathways Exploited By +Ssrna Virusesmentioning

confidence: 99%

“… 128 , 129 Hence, any intervention in glycolytic pathway of host will downregulate lipogenesis leading to an inhibition in pyruvate production and will eventually prevent it from entering into TCA cycle. 129 Various glycolytic inhibitors that are designed against AMPK (AMP-activated protein kinase, the ultimate energy-sensor in eukaryotic cells which shut down ATP-consuming processes) are metformine, lipoic acid, resveratrol, ivermectin and so on. 121 Some common inhibitors targeting the host glycolytic pathway of +ssRNA viruses are listed in Table 3 .…”

Section: Host Pathways Exploited By +Ssrna Virusesmentioning

confidence: 99%

See 1 more Smart Citation

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

Mahajan

Choudhary

Kumar

2021

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

Section: Host Pathways Exploited By +Ssrna Virusesmentioning

confidence: 99%

Section: Host Pathways Exploited By +Ssrna Virusesmentioning

confidence: 99%

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

Mahajan

Choudhary

Kumar

2021

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Recently, researchers have proposed that the metabolic reprogramming of glutamine in SARS-CoV-2 can trigger pathogenesis. They further hypothesized that metabolic intervention of glutaminolysis could be an antiviral strategy for COVID-19 [47][48][49]. Although the exact underlying mechanism is unknown, our in vitro study shows that SARS-CoV-2 replication depends on both glycolysis and glutaminolysis.…”

Section: Discussionmentioning

confidence: 79%

Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity

Krishnan

Nordqvist

Ambikan

et al. 2021

Preprint

View full text Add to dashboard Cite

Viruses hijack host metabolic pathways for their replicative advantage. Several observational trans-omics analyses associated carbon and amino acid metabolism in coronavirus disease 2019 (COVID-19) severity in patients but lacked mechanistic insights. In this study, using patient- derived multi-omics data and in vitro infection assays, we aimed to understand i) role of key metabolic pathways in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reproduction and ii) its association with disease severity. Our data suggests that monocytes are key to the altered immune response during COVID-19. COVID-19 infection was associated with increased plasma glutamate levels, while glucose and mannose levels were determinants of the disease severity. Monocytes showed altered expression pattern of carbohydrate and amino acid transporters, GLUT1 and xCT respectively in severe COVID-19. Furthermore, lung epithelial cells (Calu-3) showed a strong acute metabolic adaptation following infection in vitro by modulating central carbon metabolism. We found that glycolysis and glutaminolysis are essential for virus replication and blocking these metabolic pathways caused significant reduction in virus production. Taken together, our study highlights that the virus utilizes and re-wires pathways governing central carbon metabolism leading to metabolic toxicity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.

show abstract

“…The glycolytic pathway is central to the generation of citric acid cycle intermediates required to synthesize lipid components for viral entry, replication, and release from the cells [37]. Thus, 2-DG induced inhibition of glycolysis and post-translational modification has a significant impact in inhibiting the multiplication of the viruses.…”

Section: Effect Of 2-dg On Virusesmentioning

confidence: 99%

2-Deoxy-d-glucose Inhibits Replication of Novel Coronavirus (SARS-CoV-2) with Adverse Effects on Host Cell Metabolism

Malgotra¹,

Sharma²

2021

Preprint

View full text Add to dashboard Cite

The treatment of viral infections is challenging owing to the intricate structure and metabolism of the viruses. In addition, they can highjack host cellular metabolism, mutate and adapt to harsh environmental conditions. The novel coronavirus (SARS-CoV-2) displays further resilient attributes, making its eradication even more difficult. SARS-CoV-2 is an enveloped virus whose replication can be targeted by limiting the substrates available for structural incorporation. One such molecule that limits substrate availability and has received much attention lately is 2-Deoxy-d-glucose (2-DG). SARS-CoV-2 infection induces glycolysis, impairs mitochondrial function and damages the infected cells. Administration of 2-DG can inhibit increased glycolytic flux and some other metabolic processes to cause cessation of viral replication. This article provides a review of the mechanism of action and safety concerns associated with administering 2-DG in the treatment of COVID-19. The drug can have adverse effects on normal cell metabolism since it targets cells non-selectively, possibly in a dose-dependent manner. In addition, the drug has limited use in SARS-CoV-2 infection associated with stroke, hypoxic-ischemic encephalopathy, and critical illness.

show abstract

Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational

Abstract: Graphical abstract

Cited by 17 publications

References 227 publications

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity

2-Deoxy-d-glucose Inhibits Replication of Novel Coronavirus (SARS-CoV-2) with Adverse Effects on Host Cell Metabolism

Contact Info

Product

Resources

About