Nikhil Prasad Fact checked by:Thailand Medical News Team Feb 14, 2024 9 months, 1 week, 13 hours, 24 minutes ago
COVID-19 News: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed unprecedented challenges to global health systems and economies. While significant progress has been made in mitigating the spread of the virus, understanding its long-term health effects and developing effective prevention and treatment strategies remain paramount. Recent research has shed light on the potential role of bile acids, traditionally known for their role in aiding digestion and lipid absorption, in modulating the susceptibility to and severity of COVID-19. Specifically, bile acids such as ursodeoxycholic acid (UDCA) have shown promise in protecting against SARS-CoV-2 infection by inhibiting the farnesoid X receptor (FXR), a bile acid nuclear receptor. Additionally, bile acids have been implicated in regulating the expression of angiotensin-converting enzyme 2 (ACE2), the receptor through which the virus enters human cells. This
COVID-19 News report aims to provide a comprehensive review of the emerging evidence linking bile acids to COVID-19 and elucidate the underlying pathophysiological mechanisms, with a focus on bile acid receptors.
Potential mechanisms underlying the influence of bile acids on COVID-19. Bile acids play a significant role in influencing COVID-19 through four major pathways. (A) CDCA and UDCA control ACE2 expression through FXR. (B) TCA and CDCA inhibit the activity of Nsp15 to disturb the transcription of SARS-CoV-2. (C) OCA, CDCA, and UDCA inhibit SARS-CoV-2 spike protein binding to its receptors mediating viral entry to host cells. (D) UDCA increases ACE2 activity and thus relieves SARS-CoV-2-induced RAS activation. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; ACE2, angiotensin-converting enzyme 2; TCA, taurocholic acid; CDC, chenodeoxycholate; CDCA, chenodeoxycholic acid; UDC, ursodeoxycholate; UDCA, ursodeoxycholic acid; OCA, obeticholic acid; Nsp15, nonstructural protein 15; FXR, farnesoid X receptor; Ang II, angiotensin II; AT1R, angiotensin II type 1 receptor; RAS, renin-angiotensin system; MasR, Mas receptor.
Bile Acid System
Bile acids constitute a diverse group of amphipathic steroid acids that serve as the primary organic constituents of bile. They are classified into primary and secondary bile acids, with primary bile acids synthesized in hepatocytes from cholesterol via various pathways. Following synthesis, bile acids undergo conjugation with taurine or glycine to enhance their hydrophilicity and facilitate their secretion into bile. Through the enterohepatic circulation, bile acids are recycled between the liver and intestines, maintaining bile acid homeostasis. Bile acids exert their biological effects through interactions with specific receptors, including nuclear receptors such as FXR and membrane receptors like the G-protein-coupled bile acid receptor (TGR5).
Bile Acid Receptors
FXR, identified as the primary nuclear receptor responsive to bile acids, plays
a pivotal role in regulating bile acid synthesis, conjugation, and enterohepatic circulation. Activation of FXR modulates the expression of genes involved in lipid and glucose metabolism, as well as immune function. Conversely, TGR5, a membrane receptor, mediates bile acid signaling through the Gαs-adenylate cyclase-cyclic adenosine monophosphate (cAMP) pathway, influencing various physiological processes such as glucose homeostasis, energy metabolism, and inflammation. Both FXR and TGR5 have emerged as potential therapeutic targets for various diseases, including COVID-19.
Bile Acids and COVID-19
Recent studies have implicated bile acids in modulating susceptibility to and severity of SARS-CoV-2 infection. UDCA, a bile acid commonly used to treat liver diseases, has been shown to inhibit FXR activation, leading to downregulation of ACE2 expression in nasal epithelial cells. This inhibition of ACE2 expression may reduce the susceptibility of host cells to SARS-CoV-2 infection. Additionally, bile acids such as chenodeoxycholic acid (CDCA) and obeticholic acid (OCA) have demonstrated antiviral effects by interfering with viral replication and entry pathways. Furthermore, bile acids exert immunomodulatory effects, regulating inflammatory responses and potentially attenuating the cytokine storm associated with severe COVID-19.
Mechanisms of Action
The protective effects of bile acids against SARS-CoV-2 infection are mediated through multiple mechanisms. By inhibiting FXR activation, bile acids reduce ACE2 expression, thereby limiting viral entry into host cells. Moreover, bile acids have been shown to directly inhibit viral replication and binding to host cell receptors. Additionally, bile acids modulate immune responses, suppressing pro-inflammatory cytokine production and enhancing anti-viral immune defenses. These multifaceted effects highlight the potential of bile acids as therapeutic agents for COVID-19.
Therapeutic Implications
The identification of bile acids as potential modulators of SARS-CoV-2 infection opens up new avenues for therapeutic intervention. Drugs targeting bile acid receptors, such as FXR agonists or TGR5 agonists, could be repurposed for the treatment of COVID-19. Furthermore, natural compounds with bile acid-like properties, such as berberine and epigallocatechin-3-gallate, may offer alternative therapeutic strategies. Future research should focus on elucidating the specific mechanisms underlying the protective effects of bile acids and identifying novel compounds that target bile acid receptors for the treatment of COVID-19.
Conclusion
In conclusion, bile acids play a crucial role in protecting against SARS-CoV-2 infection through their interactions with bile acid receptors and modulation of immune responses. Understanding the mechanisms by which bile acids regulate COVID-19 pathogenesis holds promise for the development of novel therapeutic interventions. Further research is needed to explore the therapeutic potential of bile acid-based therapies and elucidate their specific effects on viral replication, immune modulation, and inflammatory pathways. By harnessing the therapeutic potential of bile acids, we may be able to effectively combat COVID-19 and mitigate its long-term health consequences.
The study findings were published in the peer reviewed journal: Acta Pharmaceutica Sinica B.
https://www.sciencedirect.com/science/article/pii/S2211383524000492
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