A Liver Disease Drug Could Protect Against COVID

by Christine Zhou



National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment." Bear bile is rich in Ursodeoxycholic acid (UCDA), comprising up to 40-50% of the total bile acid. [1]

UCDA, also known as ursodiol, is a secondary bile acid produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in the bile of bears. [2] UCDA is mainly used as a liver disease drug treating gallstones, primary biliary cirrhosis, and gall reflux gastritis. [3]



Figure 1: The structure of UCDA. Note: Wikipedia [2]

 

Vaccines protect people from getting COVID by training people’s immune systems to recognize and clear the SARS-CoV-2 virus. (SARS-associated coronavirus-2 (SARS-CoV-2) is the specific virus that causes COVID-19. ) However, they are not always effective in individuals with weak immune systems, or against some viral variants.

Angiotensin-converting enzyme 2 (ACE2) is a receptor protein that is found on the membrane of human cells and constitutes the main ‘doorway’ that the SARS-CoV-2 virus uses to enter and infect cells. UCDA can reduce the amount of ACE2 on the surface of cells by blocking a bile acid-sensing protein called farnesoid X receptor (FXR).

To test whether these findings could be translated to humans, scientists from the University of Cambridge tested UDCA in a pair of donated human lungs that were not suitable for transplantation. The lungs were ventilated and perfused with a blood-like fluid to keep them functioning, and then treated with either UDCA dissolved in a saline solution or just the saline solution. (Figure 2) After infection with SARS-CoV-2, the lung that received UCDA did not become infected, while the other did (Figure 3). [4]



Figure 2: Two lungs treated with either UDCA dissolved in a saline solution or just the saline solution and were both infected by SARS-CoV-2. Note: Research briefings: A liver drug reduces SARS-CoV-2 entry into cells [4]

 


Figure 3: After infection with SARS-CoV-2, the lung that received UCDA did not become infected, while the other did. Note: Research briefings: A liver drug reduces SARS-CoV-2 entry into cells [4]

 

UCDA is widely used, accessible, cost-effective, off-patent, and easy to manufacture and store. It does not require a well-functioning immune system as it does not target the immune system or the virus itself. Also, it prevents the virus from being able to escape treatment by mutating, therefore it could be effective in future coronavirus pandemics. Moreover, it can be used to prevent SARS-CoV-2 infection in high-risk unvaccinated groups.

  

References

[1]              Merit of an Ursodeoxycholic Acid Clinical Trial in COVID-19 Patients (Subbaya Subramanian et al., 2020) [online], last accessed 19 Feb 2023

https://pubmed.ncbi.nlm.nih.gov/32575350/

[2]              Wikipedia: Ursodeoxycholic acid [online], last accessed 19 Feb 2023

https://en.wikipedia.org/wiki/Ursodeoxycholic_acid

 [3]              Indications of ursodeoxycholic acid [online], last accessed 19 Feb 2023

 https://bnf.nice.org.uk/drugs/ursodeoxycholic-acid/#indications-and-dose

[4]              Research briefings: A liver drug reduces SARS-CoV-2 entry into cells [online], last accessed 19 Feb 2023

 https://www.nature.com/articles/d41586-022-04149-7

[5] Brevini, T., Maes, M., Webb, G.J. et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature (2022).

 https://www.nature.com/articles/s41586-022-05594-0#citeas


Comments