Infecting the Intestine Chip with NL63 (center column) caused many changes to the tissue, including the connections between cells (top row), the amount of apoptosis (cell death) occurring (middle row, in red), and the attachment of immune cells to the blood vessel lining. Treatment with the anticoagulant drug nafamostat (right column) helped to combat these disruptions. (Credit: Wyss Institute at Harvard University)

A full 60 percent of patients infected with SARS-CoV-2 also report gastrointestinal symptoms. Scientists have used a human intestine chip to study coronavirus infection and potential treatments in an environment that mimics the human intestine more effectively than cells grown in a dish.

The research team infected the chip with a coronavirus called NL63 that causes the common cold and, like SARS-CoV-2, uses the ACE2 receptor to enter cells, and then tested the effects of various drugs that have been proposed for treating SARS-CoV-2 infection. They found that a drug called nafamostat reduced infection while the drug remdesivir, which has been used to treat COVID-19 patients, did not reduce infection and actually damaged the intestinal tissue.

This new preclinical model could be used to identify drugs that can target GI symptoms associated with both the common cold and SARS-CoV-2 virus infections in the future. The team introduced the coronavirus NL63 into the channel lined with intestinal cells and observed what happened. The Intestine Chip did indeed show signs of infection: the layer of gut cells became “leaky” as the connections between them were compromised by the virus.

Having established that their chip could successfully model interactions between viruses, drugs, and the gut, the team tested a variety of other drugs that are taken orally including toremifene, nelfinavir, clofazimine, and fenofibrate, all of which have been shown to inhibit infection by SARS-CoV-2 and other viruses in vitro. Of those, only toremifene showed similar efficacy to nafamostat in reducing NL63 viral load.