How 2-DG by DRDO fight against COVID 19 Pandemic?

How 2DG by DRDO act as a Corona medicine? -A Review-

If you have the basics, Scroll down to read How 2DG by DRDO fight Covid infection?

The COVID 19 pandemic has hit the second wave in different parts of the world and is reporting disastrous in India. The DCGI (Drugs Controller General of India) approved emergency use of drug, 2-DG (2-deoxy-D-glucose), the new medicine for Covid 19 by DRDO, for the adjuvant treatment in moderate to severe case of Covid 19 patients, dated 08 April, 2021.

Who developed 2DG (2 deoxy-D-glucose) in India?

The INMAS (Institute of Nuclear Medicine and Allied Sciences) lab of DRDO (Defence Research and Development Organisation) in collaboration with DRL (Dr. Reddy’s Laboratories), Hyderabad developed a drug 2-deoxy-D-glucose for which the clinical trials have been found to be effective in treatment of Covid 19 Pandemic. Dr. Reddy’s Laboratories has been reported as the Industrial partner of DRDO in the production and distribution of 2DG.

What is 2DG?

2DG (2 deoxy-D-gliucose), the new anti-Covid drug by DRDO, is an analogue of glucose molecule, in which the second hydroxyl group (OH) has been replaced by hydrogen (H). As a biomolecule it cannot undergo further glycolysis or any other metabolic process inside the human cell.

Clinical Trials of 2-DG in India

DRDO has carried out the clinical trials of its new anti covid medicine, 2DG. The three phase trials waved a positive result of 2-DG as a safe and effective medicine in treating moderate and severe cases of covid patients.

Is 2DG by DRDO a clinically proven drug?

2-DG in its true sense isn’t a brand new molecule in medical science. A lot of research has been done with the molecule and found to be effective against many clinical and medical conditions. It has also been found to be inhibiting the growth of many other viruses. Now the trials by DRDO in India has resulted it as an effective adjuvant drug in the treatment of covid 19.

Laboratory experiments of DRDO Anti Covid Drug 2-DG

As per DRDO, at the times of first wave of COVID 19 pandemic in India, scientists at the INMAS-DRDO laboratories worked with CCMB (Centre for Cellular and Molecular Biology), Hyderabad to conduct the experiments on 2DG.

The positive result concluded 2DG to be effective against Covid causing SARS-CoV-2 viruses disrupting the viral replication, invitro.

Phase 2 clinical trials of 2-DG

As per the statement by DRDO on 2DG, the phase 2 clinical trials has been conducted from May 2020 lasted till October 2020 in 110 patients as two sub phases. Phase 2 (a) participated six hospitals. The dosage ranging has also been included in the experiments as phase 2 b in 11 hospitals across the country. The trials reported the drug to be effective and improved the recovery and hospital time of patients to 2.5 days.

Phase 3 clinical trials of 2-DG

Phase 3 trials of 2DG were conducted on December, 2020 to March, 2021 at 27 hospitals across the country, among 220 participants. The results showed reduced dependency of tested patients on supplement oxygen. This include patients of moderate cases and even those aged 65 and above.

How 2DG (2 deoxy-D-glucose) fight against Covid 19?

  1. 2DG inhibits the replication of virus inside human body and make infection less severe.
  2. 2DG by DRDO reduces medical oxygen dependency of patients.
  3. 2DG, the anti covid drug improves hospital and recovery time of each patient. It improved the RT-PCR negative conversion.

Hence act as a “medicine for the public health system” of India, facing the worst effect of second wave.

How 2DG inhibits Covid viral replication?

  • SAARS-CoV-2 causing covid 19, infects through its spike proteins, the varied strains of which causes the pandemic waves worst.
  • 2DG (2-deoxy-D-glucose), the new Covid 19 drug by DRDO, act as an inhibitor __of viral growth (technically viral replication) within the human body by __disrupting the formation of viral spike proteins.
  • 2DG as an analogue of normal glucose, act as a terminator of Glycolysis by which metabolic energy (ATP) is synthesized and Glycosylation, by which spike proteins (technically, glycoprotein) formation is halted.

As per DRDO, the initial trials itself showed faster recovery, and RT-PCR negative conversions. As per the official statement by GoI, “2-DG accumulates in the virus infected cells and prevents viral growth by stopping viral synthesis and energy production”.

Read simple explanation of viral infection method below for more clarity.

How 2DG reduces oxygen demand?

  • 2DG by DRDO reduces the cellular metabolism to replicate the virus.
  • Reduces viral load within the patient more fastly than those receiving primary treatment. Hence reduces risk of severity.

The phase 3 trial results by DRDO read reduced supplement oxygen demand by moderate case patients and even those aged 65 and above.

Read simple explanation of viral infection method below for more clarity.

How 2DG help public health system in India?

  • 2DG as an anti covid medicine in adjuvant therapy reduces the risk of falling to severity.
  • As per DRDO trials, adjuvant therapy using 2DG (2-deoxy-D-glucose) along with primary treatment helps the patient leave hospital 2 to 3 days earlier than those who receive only primary treatment. Each patient recovering to health makes the facilities available to next.

In its statement DRDO says phase 2 trials show improvement in vital signs of symptomatic patients, who were administered the drug, a difference of 2.5 days was seen compared to standard of care (Soc).

Clinical trial evidences for both by DRDO, using 2DG as an adjuvant will relax the health facilities in a nation like India, where the daily test positivity is surging above 4 lakhs.

Read simple explanation of viral infection method below for more clarity.

How 2DG by DRDO treat covid infection?

Simple explanation with viral infection method.

The SAARS-CoV2 virus that cause Covid 19 is a RNA virus, which multiplies in the infected human body by following steps:

  1. The virus infects cells with ACE-2 receptor (all mucosa producing cells, hence many more organs other than pulmonary system) by its spike proteins (technically, glycoproteins) protruding from the viral envelope.
  2. The viral RNA entering the human cell, use human cell machinery (organelles, enzymes, and metabolites for normal cell function) and get converted to DNA (a process called cDNA synthesis). The RNA, hence new DNA contain codes for making viral proteins.
  3. The viral DNA get attached to human cellular DNA.
  4. The DNA replicates with human DNA to many copies using the same cell machinery.
  5. DNAs get coded to viral proteins (viral envelopes, spike proteins, etc.) using the same human cell machinery. Thus numerous viral particles are produced.
  6. The RNA also contains codes to get converted from DNA to RNA.
  7. All the viral particles get assembled to form multiple infectious covid virus from each infected cells.
  8. Each of these virions then attack new human cell to form multiple copies.

Why 2-DG is used for the treatment of covid 19?

  • Once infected, the covid virus should go through different metabolic process to multiply and make new viruses.
  • This is assisted by the metabolic machinery of host cell, similar to its own metabolism.
  • Two such important metabolic steps are:

Glycolysis: process of breakdown of normal glucose for metabolic energy (ATP) generation.

Glycosylation: process of making glycans to form glycoproteins (viral spike proteins).

Both process requires metabolism of normal glucose.

So why? We can target this basic necessity to destroy the viral life cycle, right?

When 2DG by DRDO is given as an adjuvant medicine for corona virus,

  • The 2DG (2-deoxy-D-glucose) given to an infected cell instead of all normal glucose, can effectively reduce the number of virus formed.
  • It halts the glycolysis in the initial stages itself and ATP generation required for cellular metabolism fails.
  • It halts the formation of glycans which is used to form viral spike glycoproteins.

Thus, 2DG fights covid infection.

  • Cells infected by viruses will be under a surge of metabolism, which requires a lot of oxygen. Since 2DG reduces cellular metabolism and formation of viral particles, the standard demand of oxygen by infected cells will be drastically reduced.
  • The fall in the formation of new covid virus within the body considerably reduces the overall viral load in the patient. This reduces the risk of viral invasion to next cells and patient falling to severe conditions.
  • The immune system in most cases will be much more relaxed, not to enter a “dog-fight”, by which body will be much relaxed.

Thus, it reduces supplement oxygen demand.

  • The reduction in supplement oxygen demand, itself is a boost to public health systems like India.
  • Patients leaving hospital at the earliest, (even it is an hour) make the facilities available to next patient.

Since DRDO has stated clinical trial evidences of both, 2DG as an adjuvant will make the health facilities accessible to all.

How to prepare 2DG for Covid treatment?

Anti covid drug of DRDO, 2-DG can be administered as a powder form, dissolved in water and taken orally. As per the statements, the phase 2 of clinical trials of 2-DG has included the experiments for making dosage plans.

Is 2-DG abundantly available for enough medical use?

As per DRDO who conducted clinical trials of 2D-G in India, since it’s an analogue of glucose and a generic molecule, it is easy to produce, and consume. As well as DRDO claims it can be produced and made plentily available in the country.

When will the new covid medicine by DRDO, made available?

DRDO claims the new covid medicine 2-DG will be made available by 11th of May, 2021. The DRDO anti covid drug may come with an affordable and subsidy price of INR 500 to INR 600, which will finally depend on production, headed by Dr. Reddy’s Laborataries.

Is DRDO Anti Covid drug safe to use?

No harmful effect has been reported for 2DG, and it’s safe to use under the supervision of qualified doctors. DRDO also states the trials were done on Covid patients of all stages, and they got only benefits, no side effects were noticed.

Since many research has been done on this molecule, the data about the molecule is vast and many studies support the safety and tolerability of 2-DG in humans.

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