Gut infection expresses high levels of the ACE2 receptor protein, which COVID-19 virus uses to enter cells, is correlated with more severe cases of COVID-19, but the exact interactions between the virus and intestinal tissue are difficult to study in human patients.
To solve this problem, researchers developed a human Intestine Chip. The Intestine Chip is a device about the size of a USB memory stick made of a clear, flexible polymer through which run two parallel channels: one lined with human blood vessel cells, the other with human intestinal lining cells.
A permeable membrane between the two channels ensures that the cells can exchange molecular messengers and that substances can be delivered into the blood via the gut, mimicking digestion.
The tissues in the Intestine Chip are continuously stretched and released to recreate the rhythmic movements caused by muscle contractions in the GI tract.
Later they introduced the coronavirus NL63 into the channel lined with intestinal cells and observed what happened. The Intestine Chip showed signs of infection such as a leak between the two channels.
To find out the cure, researchers administered nafamostat, a short-acting anticoagulant drug, into the channel lined with blood vessel cells to mimic a human being injected with the drug.
Nafamostat is a known inhibitor of a class of proteins present in the gut. After administrating this drug the amount of virus present in the Intestine Chip reduced but it did not restore the integrity of the connections between the cells.
Then they tried the same experiment using remdesivir, an antiviral drug that received Emergency Use Authorization from the US Food and Drug Administration for use in treating COVID-19.
To their surprise, they found that remdesivir did not reduce the amount of virus in the Intestine Chip, and it also damaged the cells in the blood vessel channel, causing them to detach almost completely from the channel wall.
Later they 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 viral load.
These findings show that the new chip 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.
Source: Medindia
