2-Deoxy-D-Glucose (2-DG)

Introduction:

2-Deoxy-d-glucose is glucose molecule that cannot undergo glycolysis as the 2-hydroxyl group is replaced by a hydrogen (H) molecule. The glucose transporters of the cells take this drug, and the cells with higher glucose uptake take the higher amounts of 2-Deoxy-d-glucose and inhibit the production of glucose. But the exact mechanism of inhibition of cell growth is not known.

2-Deoxy-d-glucose was developed in the Defence Research and Development Organization (DRDO) laboratory, jointly by the Institute of Nuclear Medicine and Allied Sciences in collaboration with Dr. Reddy's laboratories in Hyderabad in the context of radiation therapy for cancer. This drug was approved for emergency use authorization on May 18, 2021, in India as an adjunct therapy in moderate to severe COVID-19 patients by the Drugs Controller General of India (DCGI).

The combination of 2-DG and its derivative medicines with other therapeutic modalities is a promising strategy for disrupting the viral life cycle. This helps in decreasing the development of drug resistance, and also it may lower the concentration at which a given medicine is effective, potentially lessening side effects.

Synonyms:

1. 2-DG.

2. 2-Deoxyglucose.

3. 2-Deoxy-D-arabino-hexose.

4. 2-Deoxy-D-Mannose.

What Is 2-Deoxy-D-Glucose?

The 2-deoxy-d-glucose has historically been used in the radiolabeled form to determine glucose metabolism and is also used to test cancer patients, but till now, it is an unapproved drug for cancer, viral infections, and epilepsy. However, for COVID-19 disease, the drug showed effective results. The drug starts to accumulate in the virus-infected cells and stops the viral synthesis, and because of its selective accumulation in virally infected cells, this drug is considered unique.

The basic mechanism of 2-deoxy-d-glucose is to inhibit glycolysis, and so it is still being used as an investigational drug to kill cancer cells and virus cells. For instance, during the pandemic in India, efforts were made to explore the possibilities of using this drug to defeat the COVID-19 disease. The tests at the centers of Hyderabad indicated that 2-deoxy-d-glucose killed virus cells, after which it progressed to trials in people.

What Are the Uses of 2-Deoxy-D-Glucose?

Therapeutic Drug:

2-Deoxy-d-glucose is known for its radiolabelled form. Radiolabelled 2-deoxy-d-glucose determines glucose metabolism in the following diseases as the glucose is altered in,

• Cardiovascular disease.

• Tumors.

• Alzheimer's disease.

It has been used as an adjunct to chemotherapy and radiotherapy in the treatment of,

• Lung tumors.

• Breast tumors.

• Pancreatic tumors.

• Head and neck tumors.

• Gastric tumors.

Investigational Drug:

• Anticancer Therapy - In hypoxic cancer cells, 2-deoxy-d-glucose inhibits glycolysis and prevents ATP production, that is, ultimately, cell survival.

• Antiviral Therapy - 2-Deoxy-d-glucose is effective against the herpes simplex virus (HSV) as it affects the ability of the virus to penetrate cells.

• Anticonvulsant Therapy - 2-Deoxy-d-glucose worked in the experimental trials as an anticonvulsant in temporal lobe epilepsy by suppressing certain proteins that are at high levels after a seizure.

It has been used as an experimental drug in these cases and has not been approved as a therapeutic agent.

What Is the Role of 2-Deoxy-D-Glucose in COVID Patients?

An anti-COVID oral medicine known as 2-deoxy-d-glucose was granted emergency use approval by the Drug Controller General of India (DCGI). It is used as an adjunct therapy in moderate to severely infected COVID-19 patients. This medicine has been identified to reduce supplemental oxygen dependence in hospitalized COVID-19 patients with faster recovery.

Who Are All Indicated for 2-Deoxy-D-Glucose With COVID-19 Infection?

1. 2-Deoxy-d-glucose is used in people with COVID-19 disease.

2. It should be used in the individuals:

• Only with moderate to severe COVID-19 infection.
• With increased supplemental oxygen dependence.
• Hospitalized patients due to COVID-19 infection (faster recovery).

3. This supplement is currently not used in children. Clinical trials are still being conducted to test the safety and efficacy of the supplement in children as it is not yet established.

How Effective Is 2-Deoxy-D-Glucose on COVID Patients?

2-Deoxy-d-glucose medicine structurally resembles glucose. It is now found to kill the virus causing COVID-19 disease.

Normally, the virus makes use of glucose to produce enough energy, and the produced energy helps in the multiplication of the virus.

But when the COVID-19 patients take this medicine, it is readily absorbed by the virus. Thus, the virus-infected cells start to utilize the medicine and stop the energy production by inhibiting the virus from making copies of itself. This inhibition of virus multiplication and killing helps to,

• Clear the infection.

• Prevent complications in patients even if it has spread to the lungs.

• Reduces the usage of supplemental oxygen in both moderate to severely infected COVID-19 patients.

Available Forms of 2-Deoxy-D-Glucose:

2-Deoxy-d-Glucose medicine is available in powder form, which comes in a sachet.

2-Deoxy-D-Glucose Dosage:

It is taken twice a day orally by dissolving in water. However, to get cured completely, COVID-19 patients are instructed to take this drug for a week or 5 days. Most importantly, it should be taken when only prescribed by the doctor to avoid unwanted side effects.

2-Deoxy-D-Glucose the Safe Medicine:

2-Deoxy-d-glucose has been authorized to be used across India as the Drug Controller General of India (DCGI) has given emergency use approval knowing the medicine's quality, safety (do not cause side effects under recommended doses), and efficacy. In clinical trials, 2-deoxy-d-glucose is considered to be safe if used under the doctor's advised dose and duration. Do not skip the dose and take medicine as directed by the doctor. Reach the doctor if abnormal symptoms or side effects (rare) occur, and follow the doctor's instructions carefully.

2-Deoxy-D-Glucose Efficacy:

• It provides a faster recovery in hospitalized patients and helps to reduce supplemental oxygen dependence.

• 2-Deoxy-d-glucose has been shown to work efficiently in COVID-19 patients and showed faster symptomatic cure than Standard of Care (SoC).

• A larger population improved symptomatically on the 3 rd day of taking the drug and became free from supplemental oxygen dependence (42 percent versus 31 percent ) in comparison to SoC.

Why Is 2-Deoxy-D-Glucose Considered Unique In COVID-19 Disease?

2-Deoxy-d-Glucose is considered a unique drug as it shows faster recovery in COVID-19 patients who are moderately and severely affected. This faster recovery and uniqueness is due to:

• Preventing the absorption of glucose by the virus.

• The accumulation of medicine in the virus-infected cells, thus killing the virus.

• It works by even killing the virus infection in the lungs, thus helping the patients with faster recovery.

Conclusion:

To conclude, 2-DG, which comes in sachets of powder for oral administration as an additional therapy, has been licensed by the Indian drug regulator for use in emergencies.The availability of this drug has came when India was grappling to cope with the devastating second wave of Coronavirus disease, and this drug has foreseen to reduce and save the lives of people from the burden of COVID-19. Even though the doctor advises to take this drug, following COVID-19 safety precautions is a must. So, do not ignore to follow the safety protocols as one got vaccinated or in case one is taking any other COVID drug said by the doctor. Always keep in mind that wearing masks, washing hands frequently, social distancing, hand sanitization, avoiding unnecessary outings, etc., are to be followed at any cost to protect oneself and others from further spread of the virus.