Multi-center collaboration aims to rapidly identify FDA-approved drugs that can prevent or treat COVID-19 infections

By Lindsay Brownell (BOSTON) ? The United States? 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 highly collaborative effort leverages the Institute?s computational drug discovery pipelines and human?Organ Chip?technologies, and has already found multiple approved compounds that show promise against the SARS-CoV-2 virus that causes COVID-19.

The team, led by Wyss Founding Director?Donald Ingber, M.D., Ph.D., is continuing to evaluate many more drugs, and lead compounds are being tested in high-throughput cell-based assays with CoV-2 virus in the lab of?Matthew Frieman, Ph.D., 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, Ph.D. at the Icahn School of Medicine at Mount Sinai for testing in COVID-19 animal models. Human Organ Chip technology is also being set up in the Frieman and tenOever labs with equipment supplied by Wyss spinout?Emulate, Inc., so that they can carry out experiments analyzing the human response to COVID-19 infection?in vitro. ?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 (SEAS), and is a co-founder of Emulate, Inc. In addition to identifying and testing compounds for potential use against the virus, the Wyss team has established relationships with the Beth Israel Deaconess Medical Center (BIDMC) 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 Harvard and MIT, which will then provide data that can be fed back into the 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 unfortunately do not survive the viral onslaught. To date, testing FDA-approved drugs to determine if they can be repurposed to treat COVID-19 has not yet 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.

We?re bringing the Wyss Institute up to par with the world?s leading drug development companies and institutions.

Ingber recognized that drug discovery efforts already underway at the Wyss Institute could be adapted to meet this need, and created the Institute?s Coronavirus Therapeutics Project Team. Composed of members with diverse skill sets from analytical chemistry to machine learning to pathophysiology and virology, the team has quickly shifted their work to focus nearly exclusively on finding and testing drugs that could potentially treat COVID-19. Ken Carlson, Ph.D., a Senior Staff Scientist at the Wyss Institute who is also the Project Lead of the Coronavirus Therapeutics Project Team, says that the pandemic has accelerated the pace of the Institute?s drug discovery and development pipeline by many months. ?The processes that we?re now putting in place are bringing the Wyss up to par with the world?s leading drug development companies and institutions, and we have the potential to even go beyond the current standard because we?re using novel approaches rather than what has typically been done by others,? said Carlson, who has more than 25 years of experience in the biopharma industry. Some of those novel approaches include three computational pipelines that the Wyss Institute has developed recently to harness the power of data analytics, machine learning, and computer science to address a number of different diseases. These different approaches are now being deployed to rapidly evaluate existing drugs for potential activity against COVID-19.