Effects of digoxin in inhibiting ACE2 and SARS-CoV-2 binding for attenuating COVID-19 in human adipocytes

Authors

  • Meity Ardiana Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • I Gde Rurus Suryawan Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • Hanestya Oky Hermawan Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • Primasitha Maharani Harsoyo Putri Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • Safira Rahma Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Dr. Iskak General Hospital, Tulungagung, Indonesia

DOI:

https://doi.org/10.13181/mji.oa.247273

Keywords:

adipocyte, digoxin, interleukin-6, SARS-CoV-2, tissue factor

Abstract

BACKGROUND Angiotensin-converting enzyme 2 (ACE2) has a role in SARS-CoV-2 incidence, and digoxin is a competitive inhibitor of SARS-CoV-2-ACE2 binding. This study aimed to investigate the effects of digoxin on SARS-CoV-2-ACE2 binding, proinflammatory cytokines, and prothrombotic factors in adipocytes of patients with COVID-19.

METHODS This in vitro study used adipocyte cultures, which were divided into negative control, positive control (SARS-CoV-2 S1 spike protein only), SARS-CoV-2 S1 spike protein with digoxin, and SARS-CoV-2 S1 spike protein with human recombinant soluble ACE2 (hrsACE2). Data were analyzed using one-way ANOVA and Pearson correlation.

RESULTS SARS-CoV-2 significantly elevated ACE2 and increased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1) compared to the negative control group (p<0.001). No SARS-CoV-2-ACE2 binding was detected in SARS-CoV-2 with digoxin and hrsACE2 groups, compared to the positive control group (0 ng/ml versus 0 ng/ml versus 36.33 [1.58] ng/ml, p<0.001). Digoxin significantly decreased IL-6 (48.94 [1.80] ng/ml versus 90.93 [4.29] ng/ml; p<0.001), TNF-α (87.65 [6.88] ng/ml versus 307.95 [57.34] ng/ml; p<0.001), TF (5.33 [0.32] ng/ml versus 6.85 [0.22] ng/ml; p<0.001), and PAI-1 levels (2.92 [0.168] ng/ml versus 4.86 [0.11] ng/ml; p<0.001), compared to positive control group. ACE2 positively correlated with IL-6 (p = 0.004, r = 0.763) and TF (p = 0.004, r = 0.768) but was not correlated with IL-1β, TNF-α, and PAI-1 levels.

CONCLUSIONS This study promoted digoxin therapy to prevent cytokine storm and thromboembolism by decreasing IL-6, TNF-α, TF, and PAI-1 in adipocyte cultured models at an early stage of COVID-19.

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Published

2024-12-03

How to Cite

1.
Ardiana M, Suryawan IGR, Hermawan HO, Putri PMH, Rahma S. Effects of digoxin in inhibiting ACE2 and SARS-CoV-2 binding for attenuating COVID-19 in human adipocytes. Med J Indones [Internet]. 2024Dec.3 [cited 2024Dec.5];33(3):136-40. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/7273

Issue

Section

Basic Medical Research
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