2-DG ResearchLampidis NewsMedical Research

Increased Glucose Uptake of Viral-infected Cells Suggests 2-DG Could Be Effective in the Fight Against COVID-19

From PET scan results to molecular biology data, it has long been known that increased glucose metabolism is a common trait of cancerous cells. More recently, however, viral-infected cells have also been found to increase their glucose uptake. In both cases, using carbon tracer experiments and mass spectrometry, glucose has been shown to be the molecule that provides the building blocks required to make more cancer cells and viral particles, respectively.

As an analog of glucose, 2-DG (2-deoxy-D-glucose) becomes a possible candidate for COVID-19 treatment by exploiting its preferential uptake in infected cells. 2-DG has also been shown to have anti-inflammatory effects that may benefit COVID-19 patients, especially in the latter phase of their disease. In a preliminary experiment completed on March 20, 2020, in the UK before the lab was closed in the national lockdown, 2-DG lowered the viral load by 1-2 logs in avian coronavirus infected cells in vitro at 3 and 10 mM.

Another advantage of 2-DG is its ability to block the replication of a variety of viral types by a number of different mechanisms which include the following:

  • Incorporating falsely into the structure of the viral capsid (head), leading to attenuation of its ability to become a fully infectious virus
  • Interfering with normal glycoprotein folding in the endoplasmic reticulum (ER) leads to ER stress blocking viral replication by activating the unfolded protein response and shutting down protein synthesis
  • By inhibiting glycolysis, 2-DG shuts off the building blocks required for a virus to replicate

Until today, however, there was no reliable data on how 2-DG would affect COVID-19. Using what is known as “in silico molecular modeling” (a non-cellular method which predicts how a drug will bind to its target and therefore inhibit its function), it has been shown that the structure of 2-DG fits into several of the binding sites that allow COVID-19 to attach as well as to replicate once it gets into a cell.

This is the first published report that directly examines the COVID-19 sites that 2-DG could have significant anti-viral activity on. It predicts that 2-DG will interfere with viral pathogenesis by binding what is known as its protease as well as its endoribonuclease. Each of these sites is required for proper viral replication and infectivity.

Moreover, the authors show that the docking of 2-DG with the main protease 3CLpro and NSP15 endoribonuclease of COVID-19 is significantly better than that of the standard anti-viral drugs lopinavir and favipiravir.

This recent publication together with the anti-viral activity of 2-DG previously reported in a number of different virus types, as well as via a number of different mechanisms by which it inhibits viral replication, adds further support to the call for 2-DG to be tested against COVID-19 live virus. We are aware of several such experiments currently taking place around the world – watch this space for further updates!