While other cancer researchers had to temporarily close their labs in March due to the COVID-19 pandemic, Isaac Harris, Ph.D., and Josh Munger, Ph.D., shifted their focus to the contagion that has reshaped the world.
Using their specialized knowledge of viruses and genomics technology at the Wilmot Cancer Institute, the duo is searching for new and existing, U.S Food and Drug Administration-approved medications that could block the coronavirus.
They’ve tested 624 drugs on thousands of human lung cells infected with a strain of the coronavirus to see if the drugs have any impact. So far, they’ve discovered 15 potential compounds that appear to have anti-viral activity. Their criteria for a “hit” is for the drug to block 50 percent of virus-induced cell death. The team is validating the 15 drugs and trying to understand the mechanisms behind their potential anti-viral activity, Harris said.
We’re all in this together and as we all look for ways to stop the coronavirus, the more evidence we can generate on potential treatments, the quicker that can happen.
This type of research is known as high-throughput drug screening – a process that plays a big role in drug discovery in modern medicine. But instead of finding a new drug, here, investigators are looking to repurpose existing, available drugs for treatment of the coronavirus. This involves using automated, robotic equipment to match drug candidates with cellular events that occur during disease transformation. This form of drug-screening is often less expensive and faster than developing treatments from scratch.
COVID-19 has killed 115,000 people in the United States, more than 24,000 in New York state and 222 people in Monroe County as of June 11, 2020. No vaccine and few viable treatments available, although fast-paced research is occurring on every front.
Globally, other scientists are also using high-throughput drug discovery techniques to conduct coronavirus research. But in most cases, they are looking for treatments that target the virus directly. Munger suggested the Wilmot team should look in another direction: at the cellular enzymes that fuel the thousands of biochemical reactions that cells use to convert nutrients into energy and cell growth; these reactions are what viruses hijack to produce millions of viral offspring. Known as cellular metabolism, this is Munger’s investigative specialty, which he has been studying in connection with viral infection and cancer for years. Now, he’s discovering that it might be possible to target and block some of the key enzymes involved in coronavirus cell metabolism.
“We might have a unique approach,” Munger said, “but if we find something that someone else is seeing, too, then that’s also helpful. It will be further confirmation of the science. We’re all in this together and as we all look for ways to stop the coronavirus, the more evidence we can generate on potential treatments, the quicker that can happen.”
Harris also emphasized that their drug-discovery process is more advanced, as it evaluates the effectiveness of each drug in 10 different concentrations, simultaneously. This allows the team to focus on doses that can block the virus from reproducing, while not being toxic to uninfected cells.
“We’re trying to figure out two problems at once, said Harris, who was recently recruited to Wilmot from Harvard Medical School. “Maybe at a lower dose you could still block the virus but have fewer side effects.”
Munger and Harris are buoyed by team science and the collaboration that’s occurring across the globe and at the University of Rochester Medical Center, where dozens of others are working together on coronavirus research projects and clinical trials.
“It doesn’t matter who comes in first, Harris said. “We need evidence, and fast.”
In addition to COVID-19, Harris’ primary focus is on breast cancer research. His cancer lab is back in business, and he will continue to work on both projects. Harris recently received funding from the local Breast Cancer Coalition of Rochester (BCCR) and the national 2020 Breast Cancer Research Foundation-AACR Career Development Award, to continue the cancer research.