Carolyn Bramante isn’t ready to put the pandemic behind her quite yet.

As parts of the world embrace a return to post-vaccination normalcy, Bramante and a team of University of Minnesota Medical School researchers remain committed to thwarting COVID-19’s continued threat.

“Many places around the globe won’t have vaccines available for a year or more,” says Bramante, an assistant professor of medicine. “Young children are not yet vaccinated, and variants of COVID may develop that can escape the vaccines. So people will still get it, and that’s why we still need treatment options.”

The group is on the hunt for safe, widely used medications that may help stymie the virus’s worst effects. One option may be metformin, a drug used to treat diabetes. Metformin emerged as a potential COVID-19 foe thanks to a multidisciplinary research effort that started with David Odde, a professor in the College of Science and Engineering’s Department of Biomedical Engineering.

Big data, big possibilities

Odde uses computer models and big data to simulate life at the microscopic level. Previously, he’s predicted how cancer cells will behave under specific circumstances. For COVID-19, he set out to identify which parts of the virus might be susceptible to attack from medication.

“There are so many different drugs you could try to treat COVID-19, but you can’t feasibly test them all,” he explains. “So what do you do? We tried to answer that question by saying, ‘Theoretically, here’s what we know about cell behavior, here’s what we know about COVID-19, so where are the best opportunities for intervention?’”

Odde locked in on the virus’ protein production pathway—which plays a crucial role in cell growth—as a potential weak point. From there, Christopher Tignanelli, an assistant professor in the Department of Surgery, used a computer tool known as natural language processing to search the medical literature for examples of drugs that inhibit the mTOR pathway, which controls protein production. Metformin surfaced as one potential option.

That’s when Bramante joined the effort. She’s an obesity and diabetes specialist who’s well-versed in metformin. With Bramante on board, the team launched an initial observational study in partnership with UnitedHealth Group Research and Development to assess whether the computer models were correct in predicting metformin’s efficacy against COVID-19. The results were promising, indicating the drug may be able to decrease a person’s risk of death or hospitalization after infection.

Donor support leads to national study

Although observational studies can bolster a researcher’s hypothesis, they’re not conclusive. With support from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants through Emergent Ventures, and UnitedHealth Group, Bramante is now leading a national seven-site randomized clinical trial to test metformin and two other generic medications also identified as potential COVID-19 treatments: fluvoxamine (a common antidepressant) and ivermectin (a common antiparasitic drug).

After a COVID-19 diagnosis, study participants take one of the three drugs, a combination of them, or a placebo twice a day for 14 days. Then they track their symptoms and share them with Bramante’s team. She’s hopeful the results of the study will provide valuable information about whether metformin or another generic medication could negate COVID-19’s worst outcomes. If it does, there may be reason to think the drug also could work as a preventative medication for people exposed to the virus but not yet diagnosed.

Regardless of what information the trial yields, Bramante says the research process—one where a multidisciplinary team quickly assembles to test a promising idea—has long-term implications for medicine.

“If this trial pans out, it'll be a powerful example of how to speed up the drug development process,” she says. “If we find no effect, that is also an important contribution to the science around this pandemic.”

Justin Harris is a contributor to Legacy magazine.