2-deoxy-D-Glucose: A New Hope?

2-deoxy-D-glucose (2-DG), an easily producible Glucose analog that is proven to have faster recovery of Covid19 hospitalized patients and reduction in oxygen dependence, is likely to hit the market by end of this week in limited quantity.

2-deoxy-D-Glucose

2-Deoxy-D-Glucose is a glucose analog that is phosphorylated by hexokinase to 2-DG-P(2-deoxyglucose-phosphate) preventing further metabolism by phosphoglucose isomerase thereby inhibiting glycolysis, the rate-limiting step of glycolysis.

2-deoxy-D-Glucose, widely used as an anti-cancer agent is now found to exhibit anti-COVID-19 therapeutic application, this therapeutic application of 2-deoxy-D-Glucose was developed by the Institute of Nuclear Medicine and Allied Sciences (INMAS), a lab of Defence Research and Development Organisation (DRDO), in collaboration with Dr. Reddy’s Laboratories (DRL), Hyderabad. Considering the results obtained from three phases of clinical trial DCGI(Drugs Controller General of India) granted permission for Emergency Use of this drug as an adjunct therapy in moderate to severe (stage 2 and stage 3) COVID-19 patients

How does 2-deoxy-D-Glucose work on Covid 19 Patients

Treatment with 2-deoxy-D-Glucose(2-DG) completely blocks viral replication in Covid 19-infected monocytes by interfering with its Glycolysis pathway, thereby preventing Covid 19-induced increase of ACE2 and IL-1β.

2-DG(2-deoxy-D-Glucose) treatment also inhibited Covid 19 induced TNF-α, IL-6, and IFN α, β, and λ expression in monocytes thereby reducing oxygen demand in hospitalized patients.

Source:Ministry Of Defence

Stages of Covid 19

Stage 1: Asymptomatic state (1–2 days of infection)

As the name suggests this phase does not show any major symptoms
Inhaled virus SARS-CoV-2 binds to ACE2 receptor in epithelial cells in the nasal cavity and starts replicating.
At this stage, the virus can be detected by nasal swabs.
RT-PCR value for the viral RNA is useful to predict the viral load and the progress of the disease

Stage 2: Upper airway and conducting airway response

The virus migrates down the respiratory tract along the conducting airways leading more innate immune response is triggering the release of C-X-C motif chemokine ligand 10 (CXCL-10) and interferons (IFN-β and IFN-λ) from the virus-infected cells
Symptoms are fever, malaise, and dry cough.
For 80% of the infected patients, the disease will be mild and restricted to the upper and conducting airways.

Stage 3: Lower Respiratory Tract Infection, Progression to Acute Respiratory Distress Syndrome (ARDS)

20% of the infected patients will progress to stage 3 disease and will develop pulmonary infiltrates and some of these will develop very severe disease.
The virus invades type 2 alveolar epithelial cells through host receptor ACE-2 =>undergoes replication to produce more viral Nucleocapsids.

The virus-carrying pneumocytes(surface epithelial cells of the alveoli) release many different cytokines and inflammatory markers such as interleukins (IL-1,6,8,120,12), tumor necrosis factor-α (TNF-α), IFN-λ and IFN-β, CXCL-10, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) leading to cytokine storm

Cytokine storm attracts neutrophils, CD4 helper T cells, and CD8 cytotoxic T cells, which then begin to get sequestered in the lung tissue for fighting off the virus =>this causes inflammation and lung injury=>apoptosis of host cell=>spread of viral cells to neighboring tissues

Further damage of alveolar tissues leads to ARDS

Is 2-deoxy-D-Glucose effective

Patients administered 2 DG shows a 2.5 days reduction in duration of hospital stays compared to others treated without 2 DG.

The safety and efficacy of the drug in COVID-19 patients were carried out by Defence Research Laboratory (DRL) in 3 Phases of Clinical Trials.

Phase-II trials were carried out from May to October 2020 on 110 patients who showed significant improvement in their recovery.

Phase IIa was conducted in six hospitals, Phase IIb (dose-ranging) clinical trial was conducted at 11 hospitals all over the country.

The Phase-III clinical trial was carried out on 220 patients between December 2020 to March 2021 at 27 hospitals in Delhi, Uttar Pradesh, West Bengal, Gujarat, Rajasthan, Maharashtra, Andhra Pradesh, Telangana, Karnataka, and Tamil Nadu.

In Phase III higher proportion of patients showed symptomatic improvement and became free from supplemental oxygen dependence (42%) by Day-3, indicating an early relief from Oxygen therapy/dependence.

2DG storage, dosage

The drug comes in powder form in a sachet, consumed after mixing with water, thereby making it easier for consumption

This drug is administered along with primary treatment as adjuvant therapy.

Analogue Of Glucose: Gaining Importance In Treatment Of COVID-19