An off-patent drug that is used to treat liver disease could be an “important weapon” against COVID-19, according to a new study published last night.
The research, published in *Nature*, shows ursodeoxycholic acid (UDCA) can “lock” ACE2, the doorway through which SARS-CoV-2 enters, and because it targets the host cells and not the virus, it should protect against future new variants.
Dr Fotios Sampaziotis, from the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge and Addenbrooke’s Hospital, led the research with Professor Ludovic Vallier from the Berlin Institute of Health at Charité.
Dr Sampaziotis had previously been working with organoids to study diseases of the bile ducts and found that the FXR molecule, which is present in large amounts in these bile duct organoids, directly regulates ACE2.
They found UDCA, which is used to treat primary biliary cholangitis, “turns down” FXR and closes the ACE2 doorway.
In this new study, the team went on to find they could use the same approach to close the ACE2 doorway and prevent viral infection.
It was tested successfully in hamsters exposed to the virus. Professor Andrew Owen from the University of Liverpool, who led the trial, found hamsters treated with UDCA were protected from the delta variant of the virus, which was new at the time and was partially resistant to existing vaccines.
The next stage was to test the findings in human lungs exposed to the virus.
Professor Andrew Fisher from Newcastle University and Professor Chris Watson from Addenbrooke’s hospital used a pair of donated lungs that not suitable for transplantation. Both lungs were exposed to SARS-CoV-2 and one was given UDCA and the other did not.
The lung that was given the drug did not become infected, while the other one did and when the Cambridge team worked with Professor Ansgar Lohse from the University Medical Centre Hamburg-Eppendorf, Germany, to test the drug on eight healthy volunteers to test its efficacy, they found lower levels of ACE2 when they swabbed the volunteers’ noses, which suggests the virus has fewer opportunities to break into and infect their nasal cells.
They compared data on COVID-19 outcomes from two independent cohorts of patients and found individuals who were already taking UDCA for their liver conditions were less likely to develop severe COVID-19 and be hospitalised compared to those who were not taking the drug.
Dr Sampaziotis said UDCA could be an affordable and effective way of protecting those for whom the COVID-19 vaccine is ineffective or inaccessible.
“We have used UDCA in clinic for many years, so we know it’s safe and very well tolerated, which makes administering it to individuals with high COVID-19 risk straightforward,” he said.
“This tablet costs little, can be produced in large quantities fast and easily stored or shipped, which makes it easy to rapidly deploy during outbreaks – especially against vaccine-resistant variants, when it might be the only line of protection while waiting for new vaccines to be developed. We are optimistic that this drug could become an important weapon in our fight against COVID-19.”
Brevini T, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. *Nature* 5 December 2022; doi: 10.1038/s41586-022-05594-0
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