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Bile acids and bile acid activated receptors in the treatment of Covid-19

Fiorucci et al., Biochemical Pharmacology, doi:10.1016/j.bcp.2023.115983
Dec 2023  
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Review of the potential role of bile acids and bile acid activated receptors in modulating SARS-CoV-2 infectivity and inflammation in COVID-19. Authors discuss mechanisms by which bile acids like ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), and obeticholic acid may inhibit binding of the SARS-CoV-2 spike protein to the ACE2 receptor, preventing viral entry into host cells. Additionally, bile acid receptors FXR and GPBAR1 regulate expression of ACE2, impacting susceptibility to infection, while also modulating inflammation through effects on immune pathways.
See Huang et al. for another review covering ursodeoxycholic acid for COVID-19.
Fiorucci et al., 9 Dec 2023, peer-reviewed, 6 authors. Contact: stefano.fiorucci@unipg.it.
This PaperUDCAAll
Bile acids and bile acid activated receptors in the treatment of Covid-19
Stefano Fiorucci, Ginevra Urbani, Michele Biagioli, Valentina Sepe, Eleonora Distrutti, Angela Zampella
Biochemical Pharmacology, doi:10.1016/j.bcp.2023.115983
Since its first outbreak in 2020, the pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has caused the death of almost 7 million people worldwide. Vaccines have been fundamental in disease prevention and to reduce disease severity especially in patients with comorbidities. Nevertheless, treatment of COVID-19 has been proven difficult and several approaches have failed to prevent disease onset or disease progression, particularly in patients with comorbidities. Interrogation of drug data bases has been widely used since the beginning of pandemic to repurpose existing drugs/natural substances for the prevention/treatment of COVID-19. Steroids, including bile acids such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) have shown to be promising for their potential in modulating SARS-CoV-2/host interaction. Bile acids have proven to be effective in preventing binding of spike protein with the Angiotensin Converting Enzyme II (ACE2), thus preventing virus uptake by the host cells and inhibiting its replication, as well as in indirectly modulating immune response. Additionally, the two main bile acid activated receptors, GPBAR1 and FXR, have proven effective in modulating the expression of ACE2, suggesting an indirect role for these receptors in regulating SARS-CoV-2 infectiveness and immune response. In this review we have examined how the potential of bile acids and their receptors as anti-COVID-19 therapies and how these biochemical mechanisms translate into clinical efficacy. SARS-CoV-2 SARS-CoV-2: An overview As reported by the WHO Coronavirus Dashboard (https://COVID-19. who.int), since its first outbreak in early 2020, the Coronavirus Disease 2019 (COVID-19) has resulted in the death of almost 7 million people worldwide [1] . The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the disease-causing pathogen, still wanders among the worldwide population. However, immediately implemented and still ongoing vaccination campaigns against SARS-CoV-2 have granted the transition from the initial pandemic to the current endemic phase [2] . Vaccines have been fundamental in disease prevention, and it is estimated that nearly 80 % of the world population is fully vaccinated to
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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