Researchers receive federal funding to rapidly repurpose FDA-approved drugs for COVID-19

Researchers at the University of Maryland School of Medicine (UMSOM) will be partnering on an agreement funded by the federal government's Defense Advanced Research Projects Agency (DARPA) to rapidly test hundreds of drugs, approved and marketed for other conditions, to see whether any can be repurposed to prevent or treat COVID-19. The compounds will be tested in studies using state-of-the-art technologies in the laboratory of coronavirus researcher Matthew Frieman, PhD., Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine. UMSOM will receive up to $3.6 million over the next year to fund this effort.

Other faculty from UMSOM will collaborate on this project including William Jackson, PhD, Associate Professor of Microbiology and Immunology at UMSOM, David Rasko, PhD, Professor of Microbiology and Immunology at the Institute for Genome Sciences at UMSOM, and Robert Ernst, PhD, Professor and Vice Chair of the Department of Microbial Pathogenesis in the School of Dentistry.

The funding is part of a new award totaling up to $16 million over the next year DARPA awarded to the Wyss Institute for Biologically Inspired Engineering at Harvard University, which created computational drug discovery pipelines and human Organ Chip technologies that will enable the new research.

The new technologies we now have in place in our laboratory will allow us to test more drugs at a much faster rate to determine whether they have the potential to stop the novel coronavirus from replicating in cells and causing Covid-19."  

Dr. Matthew Frieman, PhD., Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine

In a preliminary study posted last month, he and his colleagues tested 20 FDA-approved drugs and found that 17 showed promise against blocking the virus that causes COVID-19. In previous research, Dr. Frieman found these drugs also had anti-viral effects against two other deadly coronaviruses, SARS-CoV-1, which emerged in 2003 in China and MERS-CoV, which emerged in 2012 in the Middle East.

With new innovative Organ Chip technologies installed in his laboratory, Dr. Frieman and his team now plan to rapidly test dozens of drugs to determine how they interact with the virus that causes COVID-19. Organ chips are microdevices that contain human organ cells in sophisticated cell cultures; the cells replicate the function of full-size organs with tiny vasculature for fluid flow and mechanical forces to mimic the breathing motions of lungs, for example, or the filtration of kidneys.

The benchwork will include infecting human Lung Chips with the novel coronavirus to study the host responses occurring in lungs as a result of the infection. Drugs that appear to have the strongest effect at reversing these inflammatory processes in Dr. Frieman's laboratory will next be tested in animal studies.

"Through our cell and lung-on-a-chip-based anti-viral testing system, we will be able to better predict candidate therapeutics for priority testing in animal models and eventually human trials," said Dr. Frieman.

He and his collaborators will use a combined global "omics" approach to investigate the body's response to infection by SARS-CoV-2. They will study changes in gene expression and the role of certain proteins and cytokine chemicals involved in the immune response. This will be accomplished using various cell-based models, including human Organ Chips.

"We will do this during anti-viral testing to more rapidly identify and potentially increase the success of the identified drugs in future animal studies and human trials," said Dr. Ernst.

Added Dr. Rasko, "This type of interdisciplinary approach highlights the innovative and cutting-edge research at UMB and demonstrates that while we each have our own specialties, there are opportunities, such as these where we can come together to rapidly advance science."

The team is collaborating and sharing his research findings with a team at the Wyss Institute, led by Wyss Founding Director Donald Ingber, M.D., Ph.D, and with Benjamin tenOever, Ph.D. at the Icahn School of Medicine at Mount Sinai in New York. The team plans to engage with other federal entities like the Food and Drug Administration to expedite the translation of promising discoveries into effective treatments for Covid-19 patients.

"One of the bright spots that has come out of this horrible pandemic has been the acceleration of innovations by some of the most talented researchers here at the School of Medicine and elsewhere throughout the country," said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, University of Maryland School of Medicine. "Our nation is in such dire need of vaccines and therapies against Covid-19, and I am proud of our unprecedented role in these efforts."