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Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery.

Luciano Amarelle1,2, Jeremy Katzen1,3, Masahiko Shigemura1

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American Journal of Physiology. Lung Cellular and Molecular Physiology
|March 21, 2019
PubMed
Summary
This summary is machine-generated.

Cardiac glycosides (CGs) inhibit influenza A virus (IAV) replication by reducing intracellular potassium, which impairs protein translation. This mechanism offers a potential therapeutic strategy against IAV infection.

Keywords:
Na-K-ATPaseantiviral treatmentintracellular potassium

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Area of Science:

  • Virology
  • Molecular Biology
  • Pharmacology

Background:

  • Cardiac glycosides (CGs) are established treatments for cardiac failure.
  • CGs have demonstrated antiviral properties, including inhibition of viral replication.
  • The Na-K-ATPase is a key cellular target for CGs.

Purpose of the Study:

  • To investigate the mechanisms by which CGs inhibit influenza A virus (IAV) replication.
  • To determine the role of Na-K-ATPase inhibition in CG-mediated antiviral effects.
  • To assess the therapeutic potential of CGs against IAV infection.

Main Methods:

  • Studied CGs' effects on IAV replication in alveolar epithelial cells.
  • Investigated the impact of CGs on intracellular potassium levels and protein translation.
  • Utilized Na-K-ATPase-α1-sensitive mice to evaluate in vivo efficacy of ouabain treatment.

Main Results:

  • CGs inhibit IAV replication by decreasing intracellular potassium, leading to suppressed protein translation.
  • This antiviral effect is independent of viral entry, mRNA transcription, protein degradation, Src signaling, and intracellular calcium.
  • Short-term ouabain treatment prevented IAV replication without cytotoxicity in cell cultures.
  • Ouabain treatment conferred a modest survival benefit in Na-K-ATPase-α1-sensitive mice infected with IAV.

Conclusions:

  • CGs inhibit IAV replication by targeting the Na-K-ATPase and modulating cellular protein translation machinery.
  • CGs demonstrate potential as a therapeutic agent for influenza A virus infections.
  • Further research into CGs as antiviral agents is warranted.