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Published on: November 5, 2021
Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19
Junhyung Cho1, Young Jae Lee1, Je Hyoung Kim1
1Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, 28159, Chungcheongbuk-do, Republic of Korea.
Insights
Digoxin and ouabain show significant antiviral activity against SARS-CoV-2, inhibiting over 99% of viral replication. These repurposed heart medications may offer new COVID-19 treatment options, especially for patients with cardiovascular conditions.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- The COVID-19 pandemic lacks effective therapeutics, with higher mortality in patients with comorbidities like hypertension and cardiac disease.
- Drug repurposing is a viable strategy to identify antiviral agents.
- Digoxin (DIG) and ouabain (OUA), FDA-approved cardiac drugs, exhibit antiviral properties against coronaviruses.
Purpose of the Study:
- To evaluate the antiviral activity of Digoxin (DIG) and ouabain (OUA) against SARS-CoV-2 infection.
- To determine the efficacy of DIG and OUA as potential COVID-19 treatments.
Main Methods:
- Determination of half-maximal inhibitory concentrations (IC50) for DIG and OUA.
- Assessment of progeny virus titers following single-dose treatment with DIG, OUA, remdesivir, and chloroquine.
- Evaluation of viral replication inhibition at post-entry stage.
Main Results:
- DIG and OUA demonstrated antiviral activity at nanomolar concentrations.
- Single-dose treatment with DIG and OUA reduced viral titers by >99% (10^3- to 10^4-fold) at 48 hours post-infection.
- Therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, acting post-viral entry.
Conclusions:
- DIG and OUA exhibit potent antiviral effects against SARS-CoV-2.
- These cardiac drugs represent potential alternative treatments for COVID-19.
- DIG and OUA may offer additional benefits for COVID-19 patients with cardiovascular disease.
Abstract:
The 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.
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