Old Drugs and COVID-19

Multicenter collaboration to identify FDA-approved drugs for COVID-19 treatment

Researcher examines organ on chip

Wyss postdoctoral fellow Amir Bein checks a batch of human Organ Chips in the lab. Image: Wyss Institute

This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

The U.S. Defense Advanced Research Projects Agency (DARPA) has signed an agreement worth up to $16 million over the next year with the Wyss Institute for Biologically Inspired Engineering at Harvard University to identify and test FDA-approved drugs that could be repurposed to prevent or treat COVID-19.

This collaborative effort leverages the institute’s computational drug discovery pipelines and human Organs-on-Chips technologies and has already found multiple approved compounds that show promise against SARS-CoV-2, the virus that causes COVID-19.

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The team, led by Donald Ingber, founding director of the Wyss Institute, is continuing to evaluate many more drugs, and leading compounds are being tested in high-throughput cell-based assays with SARS-CoV-2 in the lab of Matthew Frieman, associate professor of microbiology and immunology at the University of Maryland School of Medicine.

The most promising drugs are being transferred to the lab of Benjamin tenOever at the Icahn School of Medicine at Mount Sinai for testing in animal models. Human Organ Chip technology is also being set up in the Frieman and tenOever labs with equipment supplied by Wyss Institute spinoff Emulate, Inc., for experiments analyzing the human response to COVID-19 infection in vitro.  

Donald Ingber is a co-founder of Emulate, Inc.

“Over the past few years, the Wyss Institute has been building up its computational approaches to identify compounds as potential therapeutics and validate them using our human Organ Chip microfluidic culture technologies, but the emergence of COVID-19 has really galvanized us to quickly integrate all of our capabilities and bring full force to bear on that challenge,” said Ingber. “Our initial successes allowed us to obtain this new support from DARPA, which we hope will greatly accelerate the development of drugs that might be used to prevent the spread of disease in large populations, as this is precisely what is needed before we can all go back to something close to life as usual.”

Ingber is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and professor of bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

In addition to identifying and testing compounds for potential use against the virus, the Wyss Institute team has established relationships with Beth Israel Deaconess Medical Center and SUNY Downstate Medical Center, where they are collecting clinical specimens from COVID-19 patients and carrying out RNA analysis using the sequencing core at the Broad Institute of MIT and Harvard. These data will then be fed back into the Wyss Institute’s computational discovery pipeline.

Computing a COVID-19 cure

There are no treatments or vaccines for this novel coronavirus because it is just that: novel. “Treatment” for those infected largely consists of supportive care so that their immune systems have the best shot at overcoming the virus on their own, but many patients do not survive the viral onslaught. To date, testing FDA-approved drugs to determine whether they can be repurposed to treat COVID-19 has not been pursued in a careful and systematic way. As a result, there has been much speculation in the media regarding unproven and/or off-label use of approved medications as potential therapies.

Ingber recognized that drug discovery efforts already underway at the Wyss Institute could be adapted to meet this need and created a coronavirus therapeutics project team. Composed of members with diverse skills from analytical chemistry to machine learning to pathophysiology and virology, the team has quickly shifted its work to focus nearly exclusively on finding and testing drugs that could potentially treat COVID-19.

 

graphic that show "computational pipelines"
Multiple computational pipelines are being used at the Wyss Institute to identify existing FDA-approved drugs that show potential activity against SARS-CoV-2. These drugs are then tested in the Frieman, Ingber and tenOever labs. Image: Wyss Institute
title slide for video: FDA-approved drug repurposing pipeline
Video: Wyss Institute