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Published on: November 5, 2021
Ursodeoxycholic acid may protect from severe acute respiratory syndrome coronavirus 2 Omicron variant by reducing
Kyungmin Lee1,2, Yujeong Na1, Minjin Kim3
1Pharmaceutical Technology Center, Daewoong Pharmaceutical Co., Ltd, Yongin-si, Gyeonggi-do, Republic of Korea.
Abstract:
The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection. UDCA is a well-known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co-housing with an Omicron variant-infected hamster group resulted in spontaneous airborne transmission, the UDCA pre-supplied group was protected from weight loss relative to the non-treated group at 4 days post-infection by more than 5%-10%. Furthermore, UDCA-treated groups had a 3-fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS-CoV-2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug-repositioning of UDCA from liver health supplement to preventive drug of SARS-CoV-2 infection.
Insights
Ursodeoxycholic acid (UDCA) offers protection against SARS-CoV-2 variants like Omicron. This bile acid reduced viral gene expression and protected hamsters from weight loss, suggesting its potential as a preventive drug.
Area of Science:
- Virology
- Pharmacology
- Immunology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, remains a global health concern.
- Existing vaccines show imperfect protection against emergent SARS-CoV-2 variants.
- The angiotensin-converting enzyme 2 (ACE2) pathway is critical in SARS-CoV-2 infection.
Purpose of the Study:
- To investigate the protective efficacy of ursodeoxycholic acid (UDCA) against the Omicron variant of SARS-CoV-2.
- To evaluate UDCA's potential as a preventive treatment for SARS-CoV-2 infections, building on prior findings with the Delta variant.
Main Methods:
- Hamsters were pre-treated with UDCA before exposure to the Omicron variant via airborne transmission.
- Weight changes, ACE2 expression in nasal cavities, and viral gene expression in the respiratory tract were monitored.
- UDCA was employed as a farnesoid X receptor (FXR) antagonist to modulate ACE2 expression.
Main Results:
- UDCA pre-treatment significantly protected hamsters from weight loss (5%-10%) compared to controls.
- UDCA treatment led to a 3-fold decrease in ACE2 expression in the nasal cavities.
- Reduced viral gene expression was observed in the respiratory tracts of UDCA-treated hamsters.
Conclusions:
- Ursodeoxycholic acid (UDCA) demonstrates protective effects against SARS-CoV-2 Omicron variant infection in a hamster model.
- UDCA effectively reduces viral load markers and prevents weight loss, indicating its potential as a preventive therapeutic.
- These findings support the drug-repositioning of UDCA from a liver health supplement to a preventive agent against SARS-CoV-2 infection.
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