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Digoxin for COVID-19

Digoxin has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Xiao et al., Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2, Frontiers in Immunology, doi:10.3389/fimmu.2020.586572
COVID-19 pandemic has infected millions of people with mortality exceeding >1 million. There is an urgent need to find therapeutic agents that can help clear the virus to prevent severe disease and death. Identifying effective and safer drugs can provide more options to treat COVID-19 infections either alone or in combination. Here, we performed a high throughput screening of approximately 1,700 US FDA-approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 20 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine besylate, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, mefloquine, and thioridazine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating a wide therapeutic window compared to hydroxychloroquine which had a safety index of 22 in similar experiments. Mechanistically, five of the effective compounds (fendiline HCl, monensin sodium salt, vortioxetine, sertraline HCl, and salifungin) were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA-approved compounds can provide much needed therapeutic options that we urgently need during the midst of the pandemic.
Jeon et al., Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs, Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.00819-20
Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC 50 s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.
Bakowski et al., Drug repurposing screens identify chemical entities for the development of COVID-19 interventions, Nature Communications, doi:10.1038/s41467-021-23328-0
AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.
MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications, Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156
Abstract Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (>65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada. Results 26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value <0.01, adjusted p-value <0.01) and beta-blockers (weighted OR 0.87, standard p-value <0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value <0.01, adjusted p-value <0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value <0.01, adjusted p-value 0.02). Conclusions Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.
Cho et al., Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19, Scientific Reports, doi:10.1038/s41598-020-72879-7
AbstractThe current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
Please send us corrections, updates, or comments. c19early involves the extraction of over 100,000 datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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