ArticleScientific reports2021
Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Allosteric Interactions of Flavonoids with ACE2 and Potential Implications for COVID-19: Computational Insights, Metabolic and Mitochondrial Effects of Rutin in A549 Cells.Cell biochemistry and biophysics · 2026Article
- Integrating Functional Response and Target Binding for Mechanism-Centered Drug Screening by High-Mass MALDI-MS.ACS central science · 2026Article
- Progress and perspectives on microbial dye remediation: enzymatic pathways, microbial diversity, and hybrid microbial-based technologies.Archives of microbiology · 2025Review
- Exploring serum and glucocorticoid-regulated kinase 1: A promising target for COVID-19 and atrial fibrillation treatment.Heart rhythm O2 · 2025Review
- Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides-A Unique Role of the Alpha3 Isoform of the NaViruses · 2025Article
- Cardiac glycosides: Looking beyond heart failure and atrial fibrillation.Indian journal of pharmacology · 2025Article
- Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities.Cell regeneration (London, England) · 2024Review
- Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.Scientific reports · 2024Article
- Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction.Molecules (Basel, Switzerland) · 2023Article
- Digoxin and Standard-of-Care Therapy for Heart Failure Patients with COVID-19: Analysis of Data from the US Military Health System (MHS) Data Repository.Drugs - real world outcomes · 2023Article
- Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD).European journal of medical research · 2022Article
- Nanoscale Technologies in the Fight against COVID-19: From Innovative Nanomaterials to Computer-Aided Discovery of Potential Antiviral Plant-Derived Drugs.Biomolecules · 2022Review
- Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.International journal of biological macromolecules · 2022Article
- Bioactive natural products in COVID-19 therapy.Frontiers in pharmacology · 2022Review
- Leveraging knowledge of Asian herbal medicine and its active compounds as COVID-19 treatment and prevention.Journal of natural medicines · 2022Review
- Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
To initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding. Here we report that ouabain, digitoxin, and digoxin, as well as sugar-free derivatives digitoxigenin and digoxigenin, are high-affinity competitive inhibitors of ACE2 binding to the Original [D614] S1 and the α/β/γ [D614G] S1 proteins. These drugs also inhibit ACE2 binding to the Original RBD, as well as to RBD proteins containing the β [E484K], Mink [Y453F] and α/β/γ [N501Y] mutations. As hypothesized, we also found that ouabain, digitoxin and digoxin blocked penetration by SARS-CoV-2 Spike-pseudotyped virus into human lung cells, and infectivity by native SARS-CoV-2. These data indicate that cardiac glycosides may block viral penetration into the target cell by first inhibiting ACE2:RBD binding. Clinical concentrations of ouabain and digitoxin are relatively safe for short term use for subjects with normal hearts. It has therefore not escaped our attention that these common cardiac medications could be deployed worldwide as inexpensive repurposed drugs for anti-COVID-19 therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.