Since the initial outbreak of the novel coronavirus in late 2019, scientific researchers across the globe have pivoted their work to focus on the current and potential future pandemics. But University of Texas researcher Jon Huibregtse has been studying proteins related to coronaviruses for the past 12 years.
“There’s a recurring theme to our research even though it may seem that we’ve jumped around from topic to topic,” says Huibregtse, a molecular biosciences professor. “It’s always been one thing leading to another — following our noses where the interesting findings lead us.”
Backed by the research they’ve done during the past decade, Huibregtse and the members of his lab recently identified a Food and Drug Administration-approved drug, 6-thioguanine, or 6-TG, and another related compound that could each be used as therapeutics to treat patients with COVID-19.
Huibregtse says they now are looking to test the drugs in clinical trials and that he is hopeful they could eventually be useful for COVID-19 patients.
“I really do think it could be brought to bear during the current pandemic,” he says.
While a vaccine is necessary to slow the spread of COVID-19, a potential therapeutic such as 6-TG, which is currently approved for use as a drug for cancer chemotherapy and chronic inflammatory diseases, could be used to help those who are already sick.
Though he has dedicated much of his career to studying tumor biology, Huibregtse actually began his research in the world of viruses. As a postdoctoral researcher at the National Cancer Institute, he studied human papillomaviruses and their association with cervical cancer.
“We made some pretty important breakthroughs in understanding there,” Huibregtse says.
This led Huibregtse to study the biochemistry of the ubiquitin proteolysis system, which is hijacked by a key papillomavirus oncoprotein, he says. Ubiquitin is a protein found in all human cells and plays an important role in regulating many cellular pathways.
“At that time, there was a lot that was still unknown,” Huibregtse says.
That led to his work on ISG15, a ubiquitin-like protein in human cells that is induced in response to viral infections. This implies, Huibregtse says, that the protein is antiviral. The coronavirus, however, has evolved a mechanism to overcome the antiviral effect of ISG15.
From that work, Huibregtse’s lab discovered that 6-TG and the related compound can block the ability of a specific coronavirus protein to interfere with the antiviral effect of ISG15, leaving the virus “dead in the water,” Huibregtse says.
Because both 6-TG and the related compound are already FDA-approved and currently administered drugs, Huibregtse and his lab will save much time normally spent on initial testing to ensure a drug is safe, nontoxic and deliverable. Huibregtse says the potential side effects of the compounds are expected to be minimal because a very low dose can inhibit viral replication.
“With a COVID-19 infection, you wouldn’t have to be treated for long periods of time,” he says. “Any side effects related to its chemotherapeutic activity probably wouldn’t show themselves over the period of time that we would be proposing to use this as a treatment.”
Huibregtse remains hopeful that his research could aid COVID-19 patients, but if not, he says, it will be important in the future nonetheless.
“When you think more long term, this is the third deadly coronavirus outbreak since 2002,” Huibregtse says. “When is the next one going to come? Even if we don’t get it to the point where (the drug) is useful in the current pandemic, it could be useful in the next.”
