According to the World Health Organization (WHO), Covid-19 infection can be asymptomatic (absence of any clinical signs and symptoms), mild (fever, dry cough, tiredness), and severe (acute pneumonia, respiratory failure, etc). In severe phase there is acute inflammation in lungs, hypoxemia, loss of perfusion, severe hypoxic vasoconstriction along with cytokine storm and excessive secretion of chemokines by immune cells.The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme II (ACE2) which facilitates the entry of virus into the host cells.

The therapeutic management of Covid-19 is done mainly through supportive care, pharmacological agents (Remdesivir, Lopinavir, Hydroxychloquine, etc.) and biological agents (monoclonal antibodies, vaccines, corticosteroids, etc).To improve the prognosis of the treatment given to the Covid patients, development of adjunct therapy was the need of the hour. The Drugs Controller General of India (DCGI) in May 2021, approved the 2-deoxy-D-glucose (2-DG) drug for emergency use as an adjunct therapy to treat moderate to severe Covid patients. This drug comes in powder form in sachet and is taken orally by dissolving it in water.

The Institute of Nuclear Medicine and Allied Sciences (INMAS) has developed the drug. This is the lab working under Defense Research and Development Organization (DRDO). In April 2020, scientists of INMAS and DRDO found that 2-deoxy-D-glucose molecule works effectively against SARS-COV-2-virus and inhibits the growth of virus. This came as a ray of hope to fight against this deadly virus and therefore, DGCI gave the permission for the further clinical trials of this drug on Covid patients.

After various clinical trials, it was observed that 2-DG drug showed faster symptomatic cure than Standard of Care (SoC) in many criteria’s. It showed that higher proportions of patient’s symptoms were improved and oxygen dependency also got reduced. This indicated the early relief from oxygen therapy

DRDO has issued the directions for usage of this drug on COVID-19 patients. According to them, ideally, 2-DG drug should be prescribed as early as possible by doctors for moderate to severe COVID-19 patients for maximum duration up to 10 days. Patients suffering from uncontrolled diabetes, severe cardiac problem, acute respiratory distress syndrome, severe hepatic and renal impairment have not been studied yet with 2-DG drug, therefore caution should be exercised. 2-DG should not be given to pregnant and lactating women and patients below 18 years of age.

Mechanism of Action
There are various immunological disturbances caused by Covid-19 infection (moderate and severe) such as decrease in CD4+ and CD8+; cytokine storm, decrease in IFNc, etc.The viral infection also results in the metabolic reprogramming of the host cells to enhance the glycolysis so that it can facilitate the viral replication and progress of infection.Therefore viral replication and its progression can be stopped by inhibiting the process of glycolysis through some potential therapeutic agents such as 2-DG drug.

-DG drug shows anti-inflammatory effects and has the potential to reduce the viral load in host cells.It also helps in improving the immune status of the Covid patients by restoring CD/CD8 ratio, enhancing NK cells and IFNc levels etc.

 

                                                   Figure 1 – Action of 2-DG on Covid infected cells

 

Figure 2 – Pharmacological action of 2-DG drug

 

Reference

1. Ierardi AM, Angileri SA, Arrichiello A, Di Meglio L, Gurgitano M, Roda GM, Carrafiello G. 2020. Pulmonary embolism in COVID-19: ventilation and perfusion computed tomography. IDCases. 21: e00805.
2. Xu ZS, Shu T, Kang L, Wu D, Zhou X, Liao BW, Sun XL, Zhou X, Wang YY. 2020. Temporal profiling of plasma cytokines, chemokines and growth factors from mild, severe and fatal COVID-19 patients. Signal Transduct Target Ther. 5(1):100.
3. Ciaglia E, Vecchione C, Puca AA. 2020. COVID-19 infection and circulating ACE2 levels: protective role in women and children. Front Pediatr. 8:206.
4. WHO Interim Guidance 2020. [Internet]. https://covid19.who.int/
5. DRDO issues directions on usage of anti-COVID drug 2-DG – The Economic Times, [Internet], https://economictimes.indiatimes.com/news/india/drdo-issues-directions-on-usage-of-anti-covid-drug-2-dg/printarticle/83147439.cms
6. DRDO Anti Covid drug 2-DG gets emergency use clearance by DGCI, [Internet], https://www.studyiq.com/
7. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, et al. 2020. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 130(5):2620–2629.
8. Thaker SK, Ch’ng J, Christofk HR. 2019. Viral hijacking of cellular metabolism. BMC Biol. 17(1):59.
9. Lampidis Foundation. 2020. Data supporting 2-DG as a possible treatment for COVID-19.
10. Choi SY, Heo MJ, Lee C, Choi YM, An IS, Bae S, An S, Jung JH. 2020. 2-deoxy-d-glucose. Ameliorates animal models of dermatitis. Biomedicines. 8(2):20
11. Bojkova D, Klann K, Koch B, Widera M, Krause D, Ciesek S, Cinatl J, Munch C. 2020. Proteomics of SARS-CoV-2-infected host cells € reveals therapy targets. Nature. 583(7816):469–472.