Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19

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.

Antiviral Activity of Digoxin and Ouabain against SARS-CoV-2 Infection and Its Implication for COVID-19

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, among patients with COVID-19, 10–40% of those with cardiac injury have more comorbidities such as acute heart failure and lymphocytopenia. An efficient strategy to response this issue is drug repurposing with expecting antiviral activity and therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases and have antiviral activity against several coronaviruses. Thus, we aimed this study to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentration (IC50) of DIG, and OUA were determined at a nanomolar concentration. Progeny virus titers of single dose treatment of DIG and OUA were approximately 103 and 104-fold lower (> 99% inhibition) than that of non-treated control or chloroquine at 48 hour post-infection (hpi). Furthermore, therapeutic treatment of DIG and OUA inhibited over 99 % of SARS-CoV-2 replication, leading to viral inhibition at post entry stage of the virus life cycle. Collectively, these results suggested that DIG and OUA could be an alternative treatment for COVID-19 with potential therapeutic effect for patients with cardiovascular disease.