We have been developing 2-deoxy-D-glucose (2-DG), an analog of glucose, as a non-toxic anti-cancer agent and in an FDA-approved Phase I clinical trial, found it to be safe in patients.

In the trial, 2-DG was used for its inhibitory effects on glycolysis, thereby shutting down increased glucose metabolism, a universal trait of many different cancer types. The shutdown of glycolysis produces energy stress on the cancer cell which provides a window of selectivity since tumor cells require more glucose than normal cells.

However, 2-DG also mimics another natural sugar, mannose, which produces another kind of stress in the cancer cell referred to as endoplasmic reticulum (ER) stress – inducing an unfolded protein response (UPR), that in turn shuts down further protein synthesis in order to alleviate this kind of stress.

Since many viruses use ER to become fully formed and infective, they have developed a means to overcome (circumvent) UPR-mediated blockage of protein synthesis, which allows them to be produced.

We reasoned that with pre- or simultaneous treatment of virally-infected cells with 2-DG, activating the UPR would shut down protein synthesis, thereby blocking viral replication. We have previously reported that our idea worked in a herpes virus known to cause cancer in AIDS patients. Subsequent publications showed that 2-DG blocks viruses that either cause lethal hemorrhagic fever in pigs or the common cold in humans.

In the latter report, investigators used a nasal spray of 2-DG to block rhinovirus replication in animal models. Since coronavirus causes similar symptoms, it would be important to test 2-DG spray in preclinical models of coronavirus. If it worked, 2-DG nasal spray could be used by humans to not only treat those infected by coronavirus, but as a prophylactic to block viral infection spread.

In this way, what is known as “herd immunity” could be achieved similar to what vaccines such as the polio vaccine have done to wipe out the disease by eliminating susceptible individuals thereby blocking further infectivity.

The dual activity of 2-DG of inhibiting glycolysis and modulating protein synthesis, offers the possibility of blocking viral replication by more than one mechanism. In the rhino virus model mentioned above, the investigators showed that inhibiting glycolysis is how 2-DG blocks viral replication. Remodeling of glucose metabolism toward a more glycolytic one is emerging as a common trait of virally-infected cells.

Similarly, cancer cells undergo a shift from oxidative phosphorylation to glycolysis in order to meet the demands of rapid growth (known as the “Warburg effect”). In other words, viruses, as well as cancer cells, use glucose not only as a vital energy source but also as the building block for further production, which has been demonstrated with carbon 13 tracer experiments and mass spectrometry.

Thus, by interfering with the increased glucose metabolism of virally-infected cells, 2-DG offers a possibility of using a proven, non-toxic, inexpensive and rapid means of treating viral outbreaks such as that of coronavirus.

Having 20+ years of experience in investigating the mechanisms by which 2-DG interferes with glucose metabolism, and interacting with investigators that are experts in herpes viral replication here at the University of Miami, and those developing 2-DG nasal spray for the common cold at the Vienna Medical Institute in Austria, and more recently with an expert in coronaviral replication in England, I believe we may have enough expertise to make an impact on this current world-wide pandemic.

Any resources that readers of this blog can contribute will be donated directly to this immediate cause.

PLEASE NOTE: As with any new treatment, safety is the first consideration and that’s exactly why FDA approved clinical trials start with a Phase I trial – to ensure safety in humans and to determine the maximum tolerated dose (MTD). So before we have people going out and using 2-DG as a possible treatment for COVID-19, we need to make sure it’s safe, using the steps that all drugs take in getting to the general public.

Anti-viral

2-DG and Coronavirus?