ALL YOU NEED TO KNOW ABOUT NEW ANTI COVID-19 DRUG- 2-DG

The Drugs controller general of India (DCGI) has approved and granted permission for the emergency use of oral drug 2-deoxy-D-glucose(2-DG) as an adjunct therapy in moderate to severe Covid-19 patients on May 01, 2021.

• Defence Minister Rajnath Singh and Union Health Minister Dr. Harsh Vardhan released the first batch of anti-COVID drug 2-deoxy-D-glucose (2-DG)

WHO DEVELOPED IT?

• The drug launched at time when the country is battling a second wave of Covid infections.
• The Institute Of Nuclear Medicine and Allied Sciences (INMAS) a lab of Defence Reasearch and Development Organisation (DRDO) has developed the drug in collaboration with Dr. Reddy’s Laboratories, Hyderabad.

WHEN AND HOW IT WAS DEVELOPED

In April 2020, during the first wave of pandemic, INMAS-DRDO scientists conducted laboratory experiments with the help of Centre for Cellular and Molecular Biology(CCMB), Hyderabad and found that this molecule works effectively against SARS-CoV-2 virus and inhibits the viral growth.

• Based on these results, Drugs Controller General of India’s (DCGI), Central Drugs Standard Control Organisation (CDSCO) permitted Phase-II clinical trail of 2-DG in COVID-19 patients in May-2020.
• The DRDO, along with its industry partner DRL, Hyderabad, started the clinical trails to test the safety and efficacy of drug in COVID-19 patients.
• In Phase-II trails conducted during May to October 2020, the drug was found to be safe in COVID-19 patients and showed significant improvement in their recovery.
• Phase IIa was conducted in 6 hospitals and Phase IIb was conducted at 11 hospitals all over the country. This was conducted on 110 patients.
• Dr. Reddy’s potential cancer drug 2-DG shows promise aganist Covid approved for Phase 3 trail but this drug is not yet approved for cancer treatment.
• As a anticancer agent, 2-DG works by preventing the supply of glucose molecules to the cancerous cells, which need glucose for survival. With the drug stopping the glucose supply, the cells start dying.
• Based on successful results, DCGI further permitted the Phase-III clinical trails in November 2020.
• This was conducted on 220 patients between December 2020 to March 2021 at 27 COVID hospitals in Delhi, Uttarpradesh, West Bengal, Andhra pradesh, Maharashtra, Telangana, Karnataka, Tamilnadu, Gujarat, Rajasthan. Data was then presented to DCGI.

HOW 2-DG HELPS THE COVID PATIENT?

2-DG is an oral drug to be administered upon prescription to hospitalised moderate to severe COVID-19 patients along with existing standard of care.

The patients treated with 2-DG showed faster symptomatic cure than Standard Of Care(SOC) on various endpoints.

A significantly favourable trend(2.5 days difference) was seen in terms of median time to achieving normalisation of specific vital signs parameters when compared to SoC.

• Patients improved symptomatically and became free from supplemental oxygen dependance by day-3.
• In comparison to SoC, 2-DG provided early relief from Oxygen therapy and dependance and ensure availability of beds for patients requiring critical care. Similar efficacy was seen in patients aged more than 65 years.
• It also prevent the rampant black marketing of oxygen equipment that has started in the wake of crisis.
• Significantly improves recovery timelines and is better than other repurposed drugs.

2-DG EFFECT IN COVID PATIENTS

• The DRDO-developed 2 DG drug which is a pseudo glucose molecule that spreads through the body like glucose.
• Stops virus from multiplying, moving to healthy cells.
• It accumulates in the virus infected cells and prevents virus growth by stopping viral synthesis and destroys the protein’s energy production. Its selective accumulation in virally infected cells makes this drug unique.
• Any virus needs glucose to survive and thrive. When the drug is given into the body, it attaches itself to the virus and stops multiplication and further spread in the body, thereby control the complications and severity.
• Oxygen deprivation and demand fuel up when there’s a high viral spread in the body, the 2DG drug inhibits growth and reduces the body’s need for further oxygen.
• It also works on virus infection spread into lungs, which helps decrease patient’s dependability on oxygen. Higher proportion of patients treated with 2-DG showed RT-PCR negative.

How will 2-DG be manufactured?

• The DRDO stated that the 2-deoxy-D-glucose (2-DG) drug being a generic molecule and analogue of glucose, it can be easily produced and made available in plenty in country.

How can 2-DG be consumed?

• The anti-COVID drug 2-DG drug comes in powder form in sachet, which is taken orally by dissolving it in water.
• A patient may have to take this drug twice a day for about five to seven days. However, it should be taken only on the advice of a doctor.

What’s the price of 2-DG?

• The final price of 2-DG not finalised yet.
• It will be determined by the DRDO partner Dr Reddy’s, which is manufacturing the medicine. It is believed to be a cheap drug.

CHEMISTRY BEHIND 2-DG

2-DG inhibit glycolysis, a process essential for the coronavirus to replicate itself and reduce the need for external oxygen.

• Glucose present in our body cells coverts to pyruvate and through this it produces energy. Through glut1 channels glucose molecules transport into the cells and phosphorylation occurs in presence of enzyme hexokinase and converts to glucose-6-p and then in presence of glucose -6-phosphate isomerase converts to fructose-6-p and then to pyruvate that produces energy.
• 2-DG is a synthetic glucose analog in which the 2-hydroxyl group is replaced by hydrogen.
• Similarly to glucose, 2-DG transported across BBB and quickly taken up into cells mainly by glucose transporters (facilitated diffusion)GLUT1 and GLUT4, although active transport via SGLT transporters also occurs. Inside the cells, 2-DG is phosphorylated to 2-deoxy-d-glucose-6-phosphate (2-DG-6-P), a charged compound that is trapped inside the cell.
• As it is missing the 2-OH group, it is unable to undergo isomerization to fructose-6-P, leading to intracellular accumulation of 2-DG-6-P within the cell, and inhibits function of hexokinase and glucose-6-phosphate isomerase enzymes and also inhibits glycolysis and glucose metabolism.
• This leads to depletion of ATP, cell cycle arrest and inhibition of cell growth, and eventually, cell death. 2-DG-6-P is product inhibitor, so cells lack energy for growing, dividing, spreading to other cells so 2-DG also used in cancer treatment as it is also non-toxic and orally available.

This is not a sole therapy but we can combine with existing therapies to kill virus infected cells, stop spreading and lower the dependency of our body cells towards oxygen.

To produce energy from glucose we need lot of oxygen so if body start utilizing glucose through glycolysis or krebs cycle or electron transport chain we need lot of oxygen so if we prevent the utilization of glucose then that amount of oxygen that our body utilizes to burn the glucose to produce energy will be decreased and all other tissues survives by this oxygen. So our dependence on oxygen will be decreased.

If we prevent our cells to take glucose and rely on other proteins that doesn’t require oxygen so oxygen dependency can be reduced.

DRAWBACKS OF 2-DG

• This drug can also kill healthy cells of our body as we are taking from oral route it spreads through all over the body as there is no targeting of drug so prevent glucose and oxygen utilization. All the organs except Kidney and liver are organs where this drug is not readily uptakable.
• Drug which is only depending on preventing utilization of glucose as a energy source is not good enough to kill a cell as cell receives different other sorts of signal to helps a cell to grow like growth factors, hormones etc. So only preventing utilization of glucose will not make a cell that much of vulnerabe that cell will die.