U-M Center for Drug Repurposing Searches for Coronavirus Therapy

Launched late last year, the Center for Drug Repurposing (UM-CDR) is already taking on the challenge of finding a drug previously approved by the FDA – or more likely a cocktail of several drugs – to battle COVID-19, the illness caused by the novel coronavirus.

A joint venture of the Michigan Institute for Clinical & Health Research (MICHR) and the Life Sciences Institute, the UM-CDR is led by Jonny Sexton, George Mashour, and Kevin Weatherwax. The UM-CDR mobilized its resources to begin rapidly identifying and screening drugs from their library of thousands that are most likely to be effective as therapeutic interventions for COVID-19 in the clinical setting. 

Assisted by artificial intelligence methods, the U-M team will begin screening all 2,400 FDA approved drugs and will extend screening to experimental compounds from a library of nearly 7,000 compounds in search of an antiviral drug or drug cocktail that is effective against COVID-19.  

Dr. Sexton discussed the UM-CDR’s efforts in an interview with Detroit’s Channel 4 on April 20. Read the full story here.

In this April 8 episode of Michigan Minds, Jonny Sexton explains how the U-M Center for Drug Repurposing is rapidly identifying and screening FDA-approved drugs that could be effective as therapeutic interventions to combat #COVID19.

These screens will identify drugs that reduce viral infection and also protect against viral-induced cell death. The UM-CDR will use the cell painting technique to evaluate drug intervention in the viral infection process – a high throughput, robotically-controlled fluorescence microscopy platform that measures thousands of features of individual cells including viral infectivity and cell health. Cell painting results in millions of highly multiplexed fluorescent images that are examined using machine vision, an artificial intelligence method trained to detect viral infection and to assess drug effects on cell health.

“Even with fast-track approval processes initiated during a pandemic, the race for a vaccine will likely take 12-18 months, so finding pre-approved drugs that might treat symptoms, reduce the length and severity of the illness, and save lives is our focus,” said Sexton, assistant professor, Internal Medicine, Michigan Medicine. “We can conduct a rapid drug screening in days.”

Jonny Sexton, PhD, assistant professor, Internal Medicine, Michigan Medicine, leads the new Center for Drug Repurposing.

Jonny Sexton, PhD, assistant professor, Internal Medicine, Michigan Medicine, leads the new Center for Drug Repurposing.

Traditional drug discovery typically involves screening hundreds of thousands of compounds to find an active substance for development. The process of bringing a novel drug to market has a very high failure rate, a timeline of 11-18 years, and costs of approximately $1-3 billion dollars. One important alternative, especially in a pandemic, is drug repurposing, which is the discovery of new uses for existing compounds that have cleared key steps in the drug development process. 

“With assistance from AI, we can now rapidly screen thousands of compounds that are most likely to help those most at risk from this illness.” said Kevin Weatherwax, Managing Director of MICHR and the UM-CDR and Adjunct Associate Clinical Professor in the College of Pharmacy. “Discoveries are unfolding hour by hour, and we hope to find the mix that works best for the growing number of patients, here and across the country.”

By focusing on FDA approved drugs, the time to enter the clinic is drastically reduced. In other viral infections, drug cocktails have been shown to increase efficacy and reduce the potential for development of acquired resistance. “I am proud to be the executive sponsor of the UM-CDR. Therapeutic options that can be rapidly translated are essential to combat COVID-19,” said George Mashour, Executive Director of MICHR and Chair of the Department of Anesthesiology.

In the words of the great Bo Schembechler, “The Team, The Team, The Team…” and the team that is working around the clock also includes Tracey Schultz, Reid Fursmidt, Jesse Wotring, Charles Zhang, Sean McCarty, Janet Follo, Matt O’Meara, Carmen Mirabelli, Carla Pretto-Kernahan, Christine Wobus, Sheya Martin, and others. 

The UM-CDR has developed a testing procedure to determine if drugs can interfere with the viral infection process or protect the host cell from viral damage. Using human bronchial epithelial cells, UM-CDR exposes them to live virus and cause a viral…

The UM-CDR has developed a testing procedure to determine if drugs can interfere with the viral infection process or protect the host cell from viral damage. Using human bronchial epithelial cells, UM-CDR exposes them to live virus and cause a viral infection. Images of the healthy cells (left) are uninfected. The cells are virally infected in the image on the right, where a red signal appears indicating the presence of infection and clear signs of cellular stress. In the lower panel using AI-based machine vision, the center classifies individual cells as positive or negative for viral infection and cell stress (all blue cells are infected). This allows them to determine if a drug will prevent infection and protect the cell from viral induced cell death.