Organ-on-a-Chip Technology Rapidly Repurposes Existing Drugs for Treatment of COVID-19

Scientists have used organ-on-a-chip (Organ Chip) technology to identify the antimalarial drug amodiaquine as a potent inhibitor of infection with SARS-CoV-2, the virus that causes COVID-19.

The Organ Chip-based drug testing ecosystem established by a collaboration spanning four research labs and hundreds of miles, led by the Wyss Institute (Boston, MA, USA), greatly streamlines the process of evaluating the safety and efficacy of existing drugs for new medical applications. It also provides a proof-of-concept for the use of Organ Chips to rapidly repurpose existing drugs for new medical applications, including future pandemics.

While many groups around the world have been testing existing drugs for efficacy against COVID-19 using cultured cells, it is well known that cells grown in a dish do not behave like the cells in a living human body, and many drugs that appear effective in lab studies do not work in patients. The Wyss team examined eight existing drugs, including hydroxychloroquine and chloroquine that they and others had found were active against SARS-CoV-2 in conventional cell culture assays.

When tested in their more sophisticated microfluidic Lung Airway Chip, which had been infected with a pseudotyped SARS-CoV-2 virus, they found that most of these drugs, including hydroxychloroquine and chloroquine, were not effective. However, another antimalarial drug, amodiaquine, was highly effective at preventing viral entry. These results were then validated in cultured cells and in a small animal model of COVID-19 using infectious SARS-CoV-2 virus. Amodiaquine is now in clinical trials for COVID-19 at multiple sites in Africa, where this drug is inexpensive and widely available. Amodiaquine is oral, extremely inexpensive, and widely available in Africa. If proven effective in these clinical trials, it could provide a badly needed weapon against COVID-19 in low-resource nations where access to vaccines and expensive new therapeutics is limited.

While the identification of amodiaquine is a major boon in fighting COVID-19, the team already has their sights set on future pandemics. In addition to SARS-CoV-2, their recent publication details their success in finding drugs that could protect against or treat several strains of influenza virus. In addition to influenza, the team is now exploring drugs that could be used against the new SARS-CoV-2 mutant strains, to suppress the dangerous “cytokine storm” that leads to many hospitalizations, and to relieve the symptoms of COVID-19 “long haulers.”

“We started testing these compounds in February 2020, had data by March, and published a preprint in April,” said senior author and Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “Thanks to the openness and collaboration that the pandemic has sparked within the scientific community, our lead drug is now being tested in humans. It’s a powerful testament to Organ Chips’ ability to accelerate preclinical testing.”

“This collaboration has allowed us to do things that we never would have had the resources to do otherwise, including recently setting up Organ Chips in our own lab so that we can now use them to study the interactions between infectious viruses and their hosts,” said Benjamin tenOever, Ph.D. at the Icahn School of Medicine at Mount Sinai. “While we’re proud of what we’ve accomplished so far for COVID-19, we’re also looking forward to studying additional virus-host dynamics using the Organ Chips in the hopes that we’ll be able to prevent or address future pandemics.”

Related Links:
Wyss Institute