DARPA taps Wyss technology to ID drugs for COVID-19 treatment

The Wyss Institute and the U.S. Defense Advanced Research Projects Agency (DARPA) have signed an agreement worth up to $16 million over the next year to use Wyss technologies to identify and test FDA-approved drugs that could be repurposed to prevent or treat COVID-19.

Specifically, DARPA will use the computational drug-discovery pipelines and human organ chip technologies developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The team, led by Wyss Founding Director Donald Ingber, has already found multiple approved compounds that show promise against the SARS-CoV-2 virus that causes COVID-19.

Many more drugs and lead compounds are being tested in high-throughput cell-based assays with native CoV-2 virus 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 COVID-19 animal models.

Human organ chip technology is also being installed in the Frieman and tenOever labs with equipment from the Wyss spinout Emulate, Inc., that will let them analyze 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 to validate them, 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, who is also 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.

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“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.”

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 the novel coronavirus because it is just that: novel.

Treatment now largely consists of supportive care to give patients’ immune systems the best shot at overcoming the virus on their own, but many patients cannot survive the viral onslaught.

To date, testing FDA-approved drugs to determine if 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.

Lung chip.
Human organ chips recapitulate the base-level functions of human organs in small cartridges that simulate conditions inside the human body. Cells in the lung chip, shown here, have characteristic hair-like cilia on their surfaces that behave like they do in vivo. Credit: Wyss Institute at Harvard University

Ingber said he recognized that drug discovery efforts already underway at the Wyss could be adapted to this end, and created a Coronavirus Therapeutics Project Team.

Composed of members with diverse skill sets, from analytical chemistry to machine learning to pathophysiology and virology, the team’s work now focuses nearly exclusively on finding and testing drugs that could potentially treat COVID-19.

“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,”

said Ken Carlson, a senior staff scientist at the Wyss and lead of the Coronavirus Therapeutics Project Team.

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The pandemic has accelerated the pace of that effort by many months, added Carlson, who has over 25 years of experience in the biopharma industry.

Some of the team’s novel approaches include three computational pipelines that the Wyss recently developed to harness the power of data analytics, machine learning, and computer science address a number of diseases. These different approaches are now being deployed to rapidly evaluate existing drugs for potential activity against COVID-19.

The first uses a proprietary machine-learning algorithm called DRUID (DRUg Indication Discoverer) developed by senior staff scientist Diogo Camacho and his team. DRUID sifts through gene-expression data generated with tens of thousands of known drug compounds and identifies those that have potential to revert a disease-state expression pattern and phenotype back to a normal one.

It was previously used to identify compounds with the potential to fight cancer and is now being used to analyze the gene-expression patterns of human lung cells infected with the CoV-2 virus, and how different drugs change those patterns.

Source
Harvard Gazette

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