Ursodeoxycholic Acid (UDCA) Can Prevent and Treat Covid-19

Scientific Research Express | Ursodeoxycholic Acid (UDCA) Can prevent and treat Covid-19



Attention! The Cambridge University Researchers Found Ursodeoxycholic Acid (UDCA) Can Prevent and Treat Covid-19

The International academic journal Nature published an article titled FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2 from the researchers on the University of Cambridge on 5th December, 2022. It suggested that the off-patent drug ursodeoxycholic acid (UDCA) could prevent the ACE2 of cells from binding the spike protein of Covid-19 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. That idea could provide a better pathway for prevention and treatment for current pandemic.
 

This research demonstrated that ACE2 acted as the main receptor for SARS-CoV-2. It identified and bound with the spike protein of virus, which is the essential for SARS-CoV-2 cellular entry and infection in human cells. And UDCA has been identifed a novel function of to control the signal of FXR to reduce ACE2 level to prevent and treat Covid-19.

UDCA through FXR regulates ACE2 in various cell types

As shown in Figure 1, the experiment results confirmed that FXR regulates ACE2 expression in 11 types of organs, including the respiratory tract, biliary tract and intestinal epithelium. what’s more, Researchers pointed out UDCA inhibited FXR signaling and reduces ACE2 levels in seven organoids derived from the respiratory, biliary and intestinal epithelium.    
 

 Figure 1: Machanism of FXR

 Figure 1: Machanism of FXR

UDCA through FXR regulates viral infection in vitro and vivo

When infected gallbladder bile duct cells, airway and intestinal organs were placed in an environment containing UDCA and one without (as shown in Figure 2), the data showed that FXR signaling in the UDCA-containing environment significantly reduced, and the infection of three organs with SARS-CoV-2 correspondently went down.  
 
Figure 2: Comparision of UDCA setting and non-UDCA setting

Figure 2: Comparision of UDCA setting and non-UDCA setting

The experiments also confirmed the need to inhibit the ACE2 protein through the regulator FXR to achieve a reduction in infection with the virus. In further studies, the data (shown in Figure 3) suggest that UDCA reduces Covid-19 virus infection through regulation by the ACE2 protein which is the practical single mechanism for UDCA making sense. Therefore, the researchers concluded that UDCA reduces the susceptibility of cells to Covid-19 in vitro through the FXR-mediated ACE2 protein.

 

Figure 3: ACE2 expression level

  Figure 3: ACE2 expression level

As for vivo experiments, researchers firstly demonstrated the decreasing of ACE2 expression when UDCA was utilized to treat infected mice and hamsters. When UDCA-injected mice were infected with Covid-19 variant Delta and dispersed to live in groups of normal uninfected mice, the infection rate for normal mice decreased by 67%, which confirmed the significant preventive effect of UDCA against COVID-19.

UDCA through FXR regulates infection in human organs

To assess the effect of UDCA, researchers surgically divided the right and the left lungs from the same donor. One was administered UDCA (UDCA lung) and another lung as a matched control receiving carrier without UDCA (control lung) to facilitate comparison. These results validate that clinical doses of circulating UDCA can downregulate ACE2 levels and reduce SARS-CoV-2 infection in human lungs ex vivo. And then the researchers observed that ‘systemic’ UDCA treatment downregulate ACE2 in the circulating perfusate and tissue likely lung parenchyma, bronchi, vessels, gallbladder epithelium) of machine-perfused organs and reduce SARS-CoV-2 infection ex vivo with the suppression of FXR signaling via systemic administration.
 

Figure 4:a pair lung comparision between two settings

Figure 4: A pair of lung comparision between two settings

UDCA reduces ACE2 in humans

Given the favorable safety profile, lack of side effects and limited cost of UDCA, 8 volunteers were recruited to be treated them with UDCA at the standard therapeutic dosage of 15 mg/kg/day26 for 5 days. The volunteers’ nasal epithelial cells were collected using 24 nasopharyngeal swabs and ACE2 levels were measured at multiple timepoints before, during and after treatment with UDCA.And results showed that in humans, UDCA reduces ACE2 levels in the nasal epithelium, which is a prime site of SARS-CoV-2 infection(as shown in Figure 5)

Figure 5: Volunteeers averaged level of ACE2

Figure 5: Volunteers averaged level of ACE2

UDCA may improve COVID-19 outcome

Patients receiving UDCA had better outcomes compared to patients not receiving UDCA, including reduced hospitalization, ICU admission and death(as shown in Figure 6). Accepting UDCA treatment, patients were less likely to develop moderate, severe or critical COVID-19according to the data of National Institute of Health COVID-19.

Figure 6: Diffferent treatments for Covid-19

Figure 6: Diffferent treatments for Covid-19

The results confirmed that UDCA treatment is not prevented from the Covid-19 side but is targeted at host-directed cells in human body from infection by regulating ACE2 expression through FXR. Base on the mechanism and clinical development of UDCA, it may be an effective primary and secondary prevention and treatment for COVID-19 and its variants in the future.

Bontac manufactures UDCA products at level of high purity, stability and safty 

The article publishing on Nature is a good piece of news about prevention and treatment of Covid-19 this year. With the exploration of new function of existing drug (UDCA) can inhibite SARS-CoV-2 entering cells. Importantly, UDCA acts on our cells and also make sense on the variant virus of Covid-19.
In addition, UDCA has been utilized in clinical treatment for many years, so it is identified safe and well tolerated, on the other hand, the raw materials and tablets products are inexpensive. And related UDCA products can be manufactured in large quantities at and convenient for store and transportation. As the researchers emphasized that we are optimistic that UDCA could be an important treatment in our fight against SARS-CoV-2.
It is no coincidence that Bontac has already researched and developed techniques of manufacturing UDCA by “whole enzyme” in 2017 and now has in stock. Enzymatic preparation of UDCA has the features of strong enzyme-catalyzed specificity, high selectivity, conversion rate >99.5%, which is a greener, less costly and more efficient production process than chemical synthesis. In terms of Bontac UDCA quality, products meet European quality standard at the level of EP10.0.
 

Product

Quality Standard

Cholic Acid

95%

Chenodeoxycholic Acid

90%+

Ursodeoxycholic acid

EP6

Ursodeoxycholic acid

EP10

 

Table: Products Quality Standard 

Brief introduction of Ursodeoxycholic acid (UDCA)

Ursodeoxycholic acid (UDCA) is a hydrophilic, non-cytotoxic bile acid, first isolated from the bile of Chinese black bears. In human bile, UDCA is a relatively low (about 1%) physiological substance. Bear bile has been used in ancient China for the treatment of liver and biliary diseases. UDCA is an FDA approved drug for the treatment of cholestatic liver disease.

UDCA Structure

CAS No.: 128-13-2

Ursodeoxycholic acid (UDCA) other efficacies

 

Protect liver cells

Chleretic action

Regulate immunity

Anti-apoptosis

Antioxidant

Lower lipid

 

 

Reference: Brevini, T., Maes, M., Webb, G.J. et al., FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2, Nature(2022)

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