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

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.

SUBMITTER: Cho J

PROVIDER: S-EPMC7530981 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Cho Junhyung J Lee Young Jae YJ Kim Je Hyoung JH Kim Sang Il SI Kim Sung Soon SS Choi Byeong-Sun BS Choi Jang-Hoon JH

Scientific reports 20201001 1

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 anti ...[more]

PMID: 33004837

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Project description:The highly contagious SARS-CoV-2 virus is primarily transmitted through respiratory droplets, aerosols, and contaminated surfaces. In addition to antiviral drugs, the decontamination of surfaces and personal protective equipment (PPE) is crucial to mitigate the spread of infection. Conventional approaches, including ultraviolet radiation, vaporized hydrogen peroxide, heat and liquid chemicals, can damage materials or lack comprehensive, effective disinfection. Consequently, alternative material-compatible and sustainable methods, such as nanomaterial coatings, are needed. Therefore, the antiviral activity of two novel zinc-oxide nanoparticles (ZnO-NP) against SARS-CoV-2 was investigated in vitro. Each nanoparticle was produced by applying highly efficient "green" synthesis techniques, which are free of fossil derivatives and use nitrate, chlorate and sulfonate salts as starting materials and whey as chelating agents. The two "green" nanomaterials differ in size distribution, with ZnO-NP-45 consisting of particles ranging from 30 nm to 60 nm and ZnO-NP-76 from 60 nm to 92 nm. Human lung epithelial cells (Calu-3) were infected with SARS-CoV-2, pre-treated in suspensions with increasing ZnO-NP concentrations up to 20 mg/mL. Both "green" materials were compared to commercially available ZnO-NP as a reference. While all three materials were active against both virus variants at concentrations of 10-20 mg/mL, ZnO-NP-45 was found to be more active than ZnO-NP-76 and the reference material, resulting in the inactivation of the Delta and Omicron SARS-CoV-2 variants by a factor of more than 106. This effect could be due to its greater total reactive surface, as evidenced by transmission electron microscopy and dynamic light scattering. Higher variations in virus inactivation were found for the latter two nanomaterials, ZnO-NP-76 and ZnO-NP-ref, which putatively may be due to secondary infections upon incomplete inactivation inside infected cells caused by insufficient NP loading of the virions. Taken together, inactivation with 20 mg/mL ZnO-NP-45 seems to have the greatest effect on both SARS-CoV-2 variants tested. Prospective ZnO-NP applications include an antiviral coating of filters or PPE to enhance user protection.

Dataset Information

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

Publications

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

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