A well-known heart drug reveals new ways to control HIV infection by limiting viral replication in infected cells.
Digoxin is a drug isolated extracted from the foxglove plant (Digitalis lanata) and has been widely prescribed for the treatment of various heart conditions. Digoxin is used in the treatment of congestive heart failure to increase heartbeat strength. However, the therapeutic effects of digoxin appear to go beyond the treatment of cardiovascular disease. Recent findings by Alan Cochrane and colleagues at the University of Toronto show that digoxin induces a dramatic inhibition in the synthesis of HIV-1 proteins in infected cells.
The team screened a panel of drugs for antiviral activity and found that digoxin significantly inhibits HIV replication in white blood cells. Using fluorescence microscopy images, the researchers were able to show a decrease in the accumulation of HIV viral ribonucleic acid (RNA) within infected cells treated with the drug. Digoxin directly interferes with RNA processing, which causes a reduction in viral RNA levels and impedes the production of new viral proteins. The study shows that digoxin specifically targets the RNA processing of the Rev gene, which is pivotal in the production of structural proteins that form new viral particles.
A new drug target in HIV treatment
Currently HIV infection is treated via antiretroviral therapies (ART), which have proven successful in slowing disease progression. However, the ability of HIV to adapt to ARTs has given rise to drug-resistant virus strains that now represent ≥16% of newly infected people. The rising adaptation of HIV to current treatments calls for the generation of new treatment strategies. Digoxin targets viral RNA processing, one of the early stages of HIV replication. Since this stage of the virus lifecycle is not targeted by current ARTs, the digoxin family of drugs represent a novel class of HIV inhibitors. Nonetheless, these promising results await further confirmation in experimental models beyond cell culture assays.
Since digoxin interrupts the viral life cycle of HIV at a stage not currently targeted by the available therapies and given this FDA-approved drug is already in clinical use, there is great potential for the development of members of the digoxin family into new ARTs for HIV infection.
Article Reference: PLoS Pathogens (doi: 10.1371/journal.ppat.1003241)