Ursodeoxycholic acid reduces ACE-2 activity in COVID-19 patients and Calu- 3 cells
Zhaowei Tong, Jianfeng Zhong, Qi Wang, Fuchu Qian, Lili Zhao, Weihong Wang, Kefeng Qin
doi:10.21203/rs.3.rs-5317838/v1
Background Reportedly, ursodeoxycholic acid (UDCA) decreases Angiotensin-converting enzyme 2 (ACE2) activities by inhibiting FXR to prevent SARS-CoV-2 infection. -19 patients (n=142, male=72, female=70) from January to May 2023 were divided into UDCA-free (n=53) and UDCA (n=89) groups and treated withnirmatasvir/ritonavir or molnupiravir for 5 days. Patients in the UDCA group were additionally given UDCA for 10 days. ACE2 was detected and clinical outcomes were assessed. Calu-3 cells were infected with the Covid-19 Spike (XBB.1.5) pseudovirusand incubated with or without UDCA.
Methods
Covid
Results On day 0 (before treatment), 3, 6, 9 (after anti-viral drug and/or UDCA treatment), ACE2 in serum and plasma in UDCA-free group was ~41 ng/ml (p=0.9962), and ~68ng/ml (p=0.6179); in UDCA group from 40.1±9.6 to 20.8±5.8 ng/ml (p=0.0000), and 68.8±15.6 to 30.2±7.7 ng/ml ( p=0.0000). In UDCA group, ACE2 mRNA in blood cells was from ~100% to 58.5±13.2% (p=0.000) on day 6 and time for fever return to normal shorter (p=0.0001). In Calu-3 cells, UDCA reduced ACE2 protein and mRNA, and blocked Covid-19 pseudovirus infection.
Conclusion UDCA reduces ACE2 activity in Covid-19 patients and Calu-3 cells, blocks Covid-19 pseudovirus infection in Calu-3 cells and improves the clinical outcomes. UDCA may be a potential drug for prevention and treatment of SARS-CoV-2 infection.
Declarations Ethics approval and consent to participate The patient part of the study was conformed to the Declaration of Helsinki (1964) and the protocol was approved by the Ethics Committee of Huzhou Central Hospital (Ethics No: 2023001-02). All human subjects and consent provided written informed consent.
Clinical Trial Clinical trial number: not applicable.
Consent for publication The Author con rms: that the work described has not been published before; that it is not under consideration for publication elsewhere; that its publication has been approved by all co-authors; that its publication has been approved by the responsible authorities at Huzhou Central Hospital where the work is carried out. The author warrants that his/her contribution is original and that he/she has full power to make this consent. The author signs for and accepts responsibility for releasing this material on behalf of any and all co-authors. The copyright transfer covers the exclusive right to reproduce and distribute the article. Author Contributions Z.T.: conceptualization, investigation, data curation, writing original draft, and project administration. J.Z.: methodology, formal analysis, resources. Q.W.: methodology, sample collection, formal analysis, investigation. F.Q.: validation, formal analysis, investigation. L. Z.: experiment operation, data analysis. W.W.: supervision, project administration, and funding acquisition. K.Q.: methodology, formal analysis, supervision, project..
References
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'abstract': '<title>Abstract</title>\n'
' <p><bold>Background</bold>\n'
'Reportedly, ursodeoxycholic acid (UDCA) decreases Angiotensin-converting enzyme 2 (ACE2) '
'activities by inhibiting FXR to prevent SARS-CoV-2 infection.\n'
'<bold>Methods</bold>\n'
'Covid-19 patients (n=142, male=72, female=70) from January to May 2023 were divided into '
'UDCA-free (n=53) and UDCA (n=89) groups and treated withnirmatasvir/ritonavir or molnupiravir '
'for 5 days. Patients in the UDCA group were additionally given UDCA for 10 days. ACE2 was '
'detected and clinical outcomes were assessed. Calu-3 cells were infected with the Covid-19 '
'Spike (XBB.1.5) pseudovirusand incubated with or without UDCA.\n'
'<bold>Results</bold>\n'
'On day 0 (before treatment), 3, 6, 9 (after anti-viral drug and/or UDCA treatment), ACE2 in '
'serum and plasma in UDCA-free group was ~41 ng/ml (<italic>p</italic>=0.9962), and ~68ng/ml '
'(<italic>p</italic>=0.6179); in UDCA group from 40.1±9.6 to 20.8±5.8 ng/ml '
'(<italic>p</italic>=0.0000), and 68.8±15.6 to 30.2±7.7 ng/ml ( <italic>p</italic>=0.0000). In '
'UDCA group, ACE2 mRNA in blood cells was from ~100% to 58.5±13.2% (<italic>p</italic>=0.000) '
'on day 6 and time for fever return to normal shorter (<italic>p</italic>=0.0001). In Calu-3 '
'cells, UDCA reduced ACE2 protein and mRNA, and blocked Covid-19 pseudovirus infection. \n'
'<bold>Conclusion</bold>\n'
'UDCA reduces ACE2 activity in Covid-19 patients and Calu-3 cells, blocks Covid-19 pseudovirus '
'infection in Calu-3 cells and improves the clinical outcomes. UDCA may be a potential drug '
'for prevention and treatment of SARS-CoV-2 infection.</p>',
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