Repurposing UDCA, an FXR Inhibitor, to Prevent SARS-Cov-2 Infection

Prayitno, Khairunnadiya; Bhat, Mamatha

doi:10.1053/j.gastro.2023.01.014

Cited by 4 publications

(4 citation statements)

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“…Since then, many efforts have been made to identify strategies to counteract cell infection by targeting virus binding to ACE2. 11 On these principles vaccines and monoclonal antibodies have been introduced in clinical practice. Based on the previously mentioned principles, therapies that modulate ACE2 expression might be also successful against different variants of SARS-CoV2 with a higher genetic barrier to resistance than vaccines and monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…Angiotensin‐converting enzyme 2 (ACE2) has been identified early in the pandemic as the entryway for SARS‐CoV‐2. Since then, many efforts have been made to identify strategies to counteract cell infection by targeting virus binding to ACE2 11 . On these principles vaccines and monoclonal antibodies have been introduced in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts

Marrone,

Covino,

Merra

et al. 2023

Liver International

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BackgroundUrsodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin‐converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID‐19.Aim and Study DesignWe retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID‐19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non‐treated subjects were assessed. The Kaplan–Meier survival analysis and log‐rank test were used to evaluate the effect of UDCA on all‐cause intra‐hospital mortality.ResultsAmong 6444 subjects with confirmed COVID‐19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no‐UDCA group and 26 (24.1%) in the UDCA group. The Kaplan–Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions.ConclusionsUDCA treatment does not appear to have significant effects on the outcome of COVID‐19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts

Marrone,

Covino,

Merra

et al. 2023

Liver International

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“…[40] The reduction in ACE2 expression by FXR inhibitors such as UDCA is considered a novel approach to prevent or treat COVID-19. [41–43]…”

Section: Decreasing Ace2 Expression Could Block Sars-cov-2 Infection ...mentioning

confidence: 99%

“…[40] The reduction in ACE2 expression by FXR inhibitors such as UDCA is considered a novel approach to prevent or treat COVID-19. [41][42][43] Notably, there is no evidence that FXR agonists increase the risk of SARS-CoV-2 infection. Instead, FXR agonists, such as obeticholic acid, chenodeoxycholic acid, fexaramine, and ivermectin, may play a critical role in COVID-19.…”

Section: Decreasing Ace2 Expression Could Block Sars-cov-2 Infection ...mentioning

confidence: 99%

Can Ursodeoxycholic Acid Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Reduce the Coronavirus Disease 2019 Severity? Current Knowledge and Unresolved Issues

et al. 2023

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A recent study revealed that the inhibition of the farnesoid X receptor using ursodeoxycholic acid (UDCA) significantly reduces angiotensin-converting enzyme 2 (ACE2) expression. Therefore, considerable attention has been paid to the use of UDCA to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reduce the severity of the disease. This review comprehensively summarizes the role of ACE2 in SARS-CoV-2 infection and the potential role and mechanisms of UDCA in the prevention of SARS-CoV-2 infection or reinfection. It also discusses unresolved issues and the potential use of UDCA in the treatment of patients with coronavirus disease.

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UDCA May Promote COVID-19 Recovery: A Cohort Study with AI-Aided Analysis

Han

et al. 2023

Preprint

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To investigate the impact of ursodeoxycholic acid (UDCA) treatment on the clinical outcome of mild and moderate COVID-19 cases, a retrospective analysis was conducted to evaluate the efficacy of UDCA on patients diagnosed with COVID-19 during the peak of the Omicron outbreak in China. This study presents promising results, demonstrating that UDCA significantly reduced the time to Body Temperature Recovery after admission and a higher daily dose seems to be associated with a better outcome without observed safety concerns. We also introduced VirtualBody, a physiologically plausible artificial neural network model, to generate an accurate depiction of the drug concentration-time curve individually, which represented the absorption, distribution, metabolism, and excretion of UDCA in each patient. It exhibits exceptional performance in modeling the complex PK-PD profile of UDCA, characterized by its endogenous and enterohepatic cycling properties, and further validates the effectiveness of UDCA as a treatment option from the drug exposure-response perspective. Our work highlights the potential of UDCA as a novel treatment option for periodic outbreaks of COVID-19 and introduces a new paradigm for PK-PD analysis in retrospective studies to provide evidence for optimal dosing strategies.

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Repurposing UDCA, an FXR Inhibitor, to Prevent SARS-Cov-2 Infection

Cited by 4 publications

References 0 publications

Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts

Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts

Can Ursodeoxycholic Acid Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Reduce the Coronavirus Disease 2019 Severity? Current Knowledge and Unresolved Issues

UDCA May Promote COVID-19 Recovery: A Cohort Study with AI-Aided Analysis

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