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Review
. 2024 May;14(5):1939-1950.
doi: 10.1016/j.apsb.2024.02.011. Epub 2024 Feb 13.

Bile acids and coronavirus disease 2019

Xiaoru Huang  1   2 , Xuening Liu  1   2 , Zijian Li  1   2   3
Affiliations
Review

Bile acids and coronavirus disease 2019

Xiaoru Huang et al. Acta Pharm Sin B. 2024 May.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been significantly alleviated. However, long-term health effects and prevention strategy remain unresolved. Thus, it is essential to explore the pathophysiological mechanisms and intervention for SARS-CoV-2 infection. Emerging research indicates a link between COVID-19 and bile acids, traditionally known for facilitating dietary fat absorption. The bile acid ursodeoxycholic acid potentially protects against SARS-CoV-2 infection by inhibiting the farnesoid X receptor, a bile acid nuclear receptor. The activation of G-protein-coupled bile acid receptor, another membrane receptor for bile acids, has also been found to regulate the expression of angiotensin-converting enzyme 2, the receptor through which the virus enters human cells. Here, we review the latest basic and clinical evidence linking bile acids to SARS-CoV-2, and reveal their complicated pathophysiological mechanisms.

Keywords: Angiotensin-converting enzyme 2; Bile acids; COVID-19; Chenodeoxycholic acid; Farnesoid X receptor; G-protein-coupled bile acid receptor; SARS-CoV-2; Ursodeoxycholic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Image 1
Graphical abstract
Figure 1
Figure 1
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.
Figure 2
Figure 2
The relationship between bile acid receptor and COVID-19. Both TGR5 (bile acid receptor 1), a membrane receptor, and FXR (bile acid receptor 2), a nuclear receptor, serve as the primary receptors for bile acids. Both receptors participate in affecting the expression of ACE2, which directly controls the entry of SARS-CoV-2 into host cells. SARS-CoV-2 infection/COVID-19 triggers immune system activation, which in some cases can lead to an excessive release of cytokines, causing cytokine storm syndrome and potentially severe complications. Bile acids regulate crucial pathways involved in immune system activation and the development of cytokine storm syndrome triggered by SARS-CoV-2, potentially contributing to the mitigation of COVID-19's clinical manifestations. BA, bile acid; FXR, farnesoid X receptor; TGR5, G-protein-coupled bile acid receptor; ACE2, angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; AKT, protein kinase B; IRF3, interferon regulatory factor 3; PKA, protein kinase A; cAMP, cyclic adenosine monophosphate; CREB, cAMP response element-binding protein; IL, interleukin; TNF-α, tumor necrosis factor-alpha; NF-κB, nuclear facto-kappa B; IκBα, NF-κB inhibitor alpha; IFN, interferon; NLRP3, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3; Treg cell, regulatory T cell; AP-1, activator protein 1; SOCS3, suppressor of cytokine signaling 3; STAT3, signal transducer and activator of transcription 3.
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