A generic drug used to treat liver disease could in the future be used to prevent covid, above all by protecting against different variants of SARS-CoV-2. A team of Cambridge scientists investigated the potential of every model available to science, from mini-organs created in the laboratory to animals, human organs and man himself. The research was published in Nature.
No entry. The molecule in question is theursodeoxycholic acid o ursodioloused to treat a chronic liver disease – primary biliary cholangitis – which affects the bile ducts, the transport routes for bile (a liquid produced by liver cells).
Fotios Sampaziotis, a hepatologist at the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge, realized quite by accident that the drug can “close the doors” on SARS-CoV-2, because tightens the ACE2 receptors that the virus uses to access our cells. It succeeds because it acts on a molecule (called FXR) very widespread on the bile ducts, which has the task of activating or deactivating this receptor.
Inhospitable host. The trump card of the drug is the ability to modify a condition of the host, i.e. man, and not of the virus: therefore it could be effective even if the virus mutates, i.e. against multiple variants of SARS-CoV-2, seen that the gate that the pathogen uses to make its way through the body is always the same ACE2 receptor.
In the new study, the scientists demonstrated that ursodiol can block not only the ACE2s of the bile ducts, but also those of the lungs and intestines, the two organs where the coronavirus spreads most pervasively.
PLAN OF ATTACK. The scientists worked at several levels: first, with the help of colleagues at the University of Liverpool, they tested the molecule on laboratory-grown lung and intestinal organoids. So on hamsters, the most used animal models for preclinical tests of anticovid drugs. Ursodiol protected rodents exposed to the Delta variant virus from infection, during the period in which this version of the coronavirus was partially resistant to vaccines.
It was then switched to human donor lungs unsuitable for transplantation, and kept alive outside the body using a lung ventilator and blood-like fluid infusion system. Both lungs were exposed to the virus, but one was treated with the drug and the other was not.
The treated one did not contract the infection: “This could prove to be important for transplants, given the risk of transmitting CoViD-19 through donated organs,” explains Andrew Fisher, a professor at the University of Newcastle who collaborated on this part of the study. work. “It could open up the possibility of treating organs pharmacologically to clean them of the virus before transplants.”
Efficacy signals in humans. With the help of colleagues at the Hamburg Eppendorf University Medical Center in Germany, the drug was finally tested on eight healthy volunteers, whose nasal swabs actually showed lower levels of ACE2. While it has not yet been possible to organize large-scale clinical trials, the study authors looked at data on covid outcomes in patients who took ursodiol for their liver condition and in patients who did not. Fewer cases of serious illness and hospitalization were found in the first group.
Complementary to vaccines. Not a small advantage, the drug is already existing, cheap, well tolerated, producible in large quantities and available in easily transportable rigid capsules.
If human trials prove effective, in the future it could work alongside vaccines in preventing covidespecially against antibody-resistant variants, or even in contexts where vaccines are still not widespread, in vulnerable patients or with an unresponsive immune system.