Organ Chips Enable Rapid Drug Repurposing

Using Organ Chips technology, researchers discovered that the antimalarial drug amodiaquine is a powerful inhibitor of infection with SARS-CoV-2, the virus that causes COVID-19.

The drug testing ecosystem greatly simplifies evaluating the safety and efficacy of existing drugs for new medical applications. It serves as a proof-of-concept for the use of Organ Chips to rapidly repurpose existing drugs for new medical applications, such as future pandemics.

The Organ Chips platform is a microfluidic device the size of a USB memory stick, with two parallel channels separated by a porous membrane. Human lung airway cells are grown in one channel perfused with air, while human blood vessel cells are grown in the other channel perfused with a liquid culture medium to mimic blood flow. Cells grown in this device naturally differentiate into multiple airway-specific cell types in proportions similar to those found in the human airway, developing characteristics in living lungs, such as cilia and the ability to produce and move mucus.

Airway Chip cells have higher levels of angiotensin-converting enzyme-2 (ACE2) receptor protein, which is important in lung physiology and is used by SARS-CoV-2 to infect cells. Armed with the SARS-CoV-2 pseudovirus, the researchers first perfused the blood vessel channel of the Airway Chips with several approved drugs, including amodiaquine, toremifene, clomiphene, chloroquine, hydroxychloroquine, arbidol, verapamil, and amiodarone, all of which have shown activity against other related viruses in previous studies.

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