Cardiotonic Steroids Suppress Adenovirus Replication

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Human adenoviruses are common pathogens that can cause life-threatening illness, yet no approved therapies are available for treatment. This work shows that two cardiotonic steroids, digoxin and digitoxin, inhibit adenovirus replication in A549 lung carcinoma cells beyond immediate early E1A expression, with reduced expression of subsequent early regions E1B, E2B and E4. This alteration in viral gene expression leads to a block in genome replication that in turn prevents late gene expression. Nuclear changes characteristic of early infection were observed in treated, infected cells. E1A expression can be reduced if cells are pre-treated with drug provided that the drug is maintained on the cells after infection. The antiviral effect is abrogated by increased extracellular concentration of potassium. Digoxin and digitoxin also inhibit adenovirus replication in primary human nasal epithelial cells. This work supports the idea that cardiotonic steroids could be developed as antiviral agents for adenovirus infections.

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