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.
Highlights
The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents
The International Committee on Taxonomy of Viruses (ICTV) named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 19 (COVID-19)[3]
In this study, we evaluated the antiviral activity of DIG and OUA based on viral growth kinetics and inhibition at different stages of viral infection, and compared it to that of vehicle (DMSO), chloroquine (CHQ) and REM to identify a suitable and potent antiviral agent to treat COVID-19 patients with cardiac diseases
Summary
The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. 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. 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. In addition to antiviral drugs based on viral protease inhibitors and nucleoside analogs, the cardiac glycoside (CG)-based drugs digoxin (DIG) and ouabain (OUA) have been shown to exhibit antiviral activity through various mechanisms against several DNA and RNA viruses, such as cytomegalovirus, herpes simplex virus, MERS-CoV, human immunodeficiency virus, respiratory syncytial virus, chikungunya virus, and the recently identified SARS-CoV-217–24
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