While the world contemplates biological warfare threats through manmade viruses, India's Defence Research and Development Organisation comes to the rescue by repurposing the 2-DG drug for COVID. At a time when India is grappling with rising cases of COVID infection with regards to the high demand for oxygen cylinders and hospital beds, DRDO has yet again come up with two excellent developments that can tackle unnecessary hospitalisation and oxygen demands.
DRDO develops strategic programs, tactical R&D that produces radars, sonars, torpedoes, missiles, aircrafts, arms & ammunitions. They also develop life support technology that has been of great use in air and on land.
With regard to COVID care, DRDO has produced ventilators, sanitisers and the drug that is soon going to be the talk of the town, 2-deoxy-D-Glucose (2-DG). They are also building a military hospital with an ICU in the battle field. These have contributed to facing challenges of COVID-19.
Dr William Selvamurthy presently working with Amity University as President of Amity Science, Technology and Innovation Foundation and Director General for Amity Directorate of Science and Innovation is a distinguished scientist and served as a Chief Controller, Research & Development (Life Sciences & International Cooperation) at Defence Research and Development Organisation, Government of India. He served in DRDO for over 40 years. In conversation with CSP, Dr Selvamurthy spoke in detail about the two developments that have been employed for COVID care that has benefitted many.
2-DG was developed by DRDO’s Institute of Nuclear Medicine and Allied Sciences (INMAS) in collaboration with Dr Reddy’s Laboratories (DRL), Hyderabad for emergency use. This drug took 20 years to develop and was initially developed to function as a radio sensitiser for cancer therapy. "When a patient is administered radiotherapy, the treatment leads to the death of not only the cancer cells but also the neighbouring healthy cells. The aim of this development was to selectively kill the cancer cells alone. DRDO employed the strategy of depleting energy sources that cancer cells are in dire and constant need for rapid replication," says Dr Selvamurthy.
How does this drug work?
2-DG is an analogue of glucose. When it is administered to the patient, it selectively targets the cancer cells. 2-DG cannot take part in the glycolysis pathway (glucose metabolism pathway). These cancer cells are unable to utilise this glucose analogue which leads to a fall in ATP (energy currency of the cell). This lack of energy ultimately leads to organelle failure and the cells die.
2-DG for COVID
This drug has now been repurposed for COVID. COVID is similar to cancer cells. "They are hyperactive and need a constant source of energy to proliferate continuously. When the virus enters the cells, it takes over the cell machinery. The energy produced in the cell is taken up by the virus for replication and proliferation at a rapid speed. When the cell is completely depleted of energy, the cell dies and releases the virus which in turn infects another cell and the cycle continues," says Dr Selvamurthy.
The strategy is to switch off the energy in the virus-infected cell. This will cause a replication arrest and a fall in virulence. When replication is arrested, immune cells of the body will take care of the virus. A classic case of synthetic lethality that is employed in many cancer drugs trials.
The cells have many energy synthesising pathways that can occur in the presence and absence of oxygen. This gives the cell to switch over to alternate pathways to produce energy. 2-DG inhibits the production of energy in both aerobic and anaerobic conditions (unlike glucose).
The drug has gone through pre-clinical, Phase I, II and III studies and was approved by the Drug Controller General of India and by the FDA. Phase I studies were conducted at Dr Reddy’s laboratory who are now in-charge of the production. Phase II had around 110 patients and Phase III had more than 200 patients. The drug will be available in powder form and will be sold in sachets. The powder can be mixed in water and taken orally.
"DRDO observed that this reduced the duration of hospitalisation of the patients. Oxygen demand could also be brought down. That said, it is not an anti-viral drug that kills and eradicates the viral load from the body. The patient must take other measures to boost their immunity that plays a major role in eradicating the virus from the body giving rise to a negative test result," Dr Selvamurthy said.
Another very important and thrilling development by DRDO is the OBOGS (On-Board Oxygen Generating System) that are of great service to COVID care. Tejas and other aircrafts that carry out intercontinental missions cannot carry tons of oxygen cylinders on-board to provide oxygen for fighter pilots. Defence Bio Engineering and Electro Medical Laboratory (DEBEL) developed a system where atmospheric air is passed through a zeolite sieve that filters nitrogen and accumulates oxygen that can be given to the pilots. The aircraft carries essential oxygen cylinders too but the oxygen that is used by the pilots on-board is produced by this generation system. While the pilot keeps flying, the atmospheric oxygen is concentrated and that is taken up the pilot. Only under emergency situations, the oxygen cylinders are used.
"DRDO has also built an oxygen enriched chamber in Ladakh which uses this concept of oxygen concentrators. Pilots can stay in the chamber when they suffer from acute mountain sickness or severe headache," says Dr Selvamurthy.
This system now finds use in hospitals for COVID care. With one OBOGS, fifty patients can be benefitted by upscaling the system (in aircrafts, one OBOGS is used by one pilot only). "When SpO2 level falls below 90, it is critical to increase the oxy-haemoglobin levels. With dipping oxygen levels, the patients’ breathing becomes short, quick and shallow. This can aggravate hypoxemia (oxy-haemoglobin levels are going down). When a patient gasps for breath, the requirement of oxygen goes up. This system developed by DRDO meets that requirement," he added.
These ground-breaking developments are the need of the hour and India’s military power is benefitting the healthcare system tremendously!