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Human organ chips enable rapid drug repurposing for COVID-19

Updated: Jun 12

Emulating the human lung airway in vitro identified the SARS-CoV2-inhibiting effects of the antimalarial drug amodiaquine, which is now in COVID-19 clinical trials

(BOSTON) — A Wyss Institute-led collaboration spanning four research labs and hundreds of miles has used the Institute’s 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 the collaboration greatly streamlines the process of evaluating the safety and efficacy of existing drugs for new medical applications, and provides a proof-of-concept for the use of Organ Chips to rapidly repurpose existing drugs for new medical applications, including future pandemics. The research is reported in Nature Biomedical Engineering.

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.

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