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

Abstract

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.

An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS‐CoV‐2 infection: A hypothesis

“…So, inhibition of glucose uptake by GLUT4 could inhibit glucose transport and viral replication (Yu et al, 2011 ). In this regard, it has been hypothesized that activation of the PI3K/AKT signaling pathway by SARS‐CoV‐2 contributes to inducing glucose uptake through GLUT‐4 leading to increase glycolysis and viral replication in host cells (Malgotra & Sharma, 2021 ). Since it has been reported that genistein is a potent and direct inhibitor of GLUT‐4 (Lewicki et al, 2018 ), the direct inhibition of GLUT‐4 by genistein from one side and inhibition of the PI3K/AKT pathway from another side could disrupt the viral replication (Figure 2 ).…”

A Comprehensive Overview on COVID-19: Future Perspectives

“…As emergency medicine, doctors are relying on oxygen therapy, extracorporeal membrane oxygenation (ECMO), glucocorticoid supplementation (Dexamethasone), a common antibiotic, and antifungal treatments (van Paassen et al, 2020). Refer to Table 1 (Han et al, 2020;Madjid et al, 2020;Zheng, 2020;Ardestani and Azizi, 2021;Malgotra and Sharma, 2021;Shamsi et al, 2021).…”

"Repurposing of Heterocyclic Compounds as Anti- COVID-19 (SARS-Cov-2) Therapeutics: A Review"

“…So, besides its therapeutic use in seizures, cancer and, viral infections, clinical trials prove its efficient use in the treatment of COVID-19 helping the faster recovery of the hospitalized patients and reducing the dependence on supplemental oxygen. 2-DG is a non-selective and dose-dependent oral administrative drug that can cause several adverse effects on the heart, platelets, adrenal medulla, and neurons [91]. However, the reports showed that its cautious and prescribed use has resulted in the RT-PCR negative conversations in the COVID-19 patients (Figure 11).…”