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

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.