Currently, there is only one class of antiviral drugs against herpesviruses––a family of viruses that causes mononucleosis, herpes, shingles, and meningitis, among other illnesses––meaning that options for treating these infections are limited. If viruses become resistant to these frontline treatments––a growing problem, particularly in clinical settings––there are no alternative drugs to serve as backup.
In a search for new drugs to treat viral infections, scientists at the University of Utah School of Medicine have found that a drug routinely used to treat heart failure––spironolactone—has the ability to block infection by Epstein–Barr virus (EBV), a herpesvirus that causes mononucleosis and is associated with several human cancers. The researchers found that the drug’s antiviral properties stem from its ability to block a key step in viral infection that is common to all herpesviruses. Spironolactone’s target is distinct from that of existing drugs, suggesting that it could be developed into a new class of anti-herpesvirus drug, according to the researchers. Their findings were published in the Proceedings of the National Academy of Sciences.
“It’s remarkable that a drug we have used safely in the clinic for over 50 years is also an effective EBV inhibitor,” said senior author Sankar Swaminathan, MD. “It goes to show how basic research can reveal things we would never have found otherwise.”
Swaminathan and his colleagues uncovered the antiviral properties of spironolactone in a screen to identify drugs that work through a mechanism that is different from that of existing anti-herpesvirus drugs. Currently available treatments block a middle step in the viral infection cycle by inhibiting the virus’ ability to replicate DNA. The investigators found that like these drugs, spironolactone can block EBV replication in cells, but it does so by targeting the SM protein, which is required for a late step in the infection cycle.
Importantly, spironolactone’s ability to block viral infection appears to be separate from its ability to treat heart failure. Previous studies have shown that the drug treats heart failure through a different metabolic mechanism. The new study found that a drug similar to spironolactone shared its ability to treat heart failure but not its antiviral properties. Together, these results suggest that the two mechanisms are separable, the authors noted.
“We think there is great potential to modify this molecule so that it can work as an antiviral without having undesired side effects,” Swaminathan explained. Spironolactone could be developed as a new medication against EBV, a common infection among transplant and other immunocompromised patients.
But because all herpesviruses depend on SM-like proteins to spread infection, the new findings also have broader implications, Swaminathan said. Spironolactone could be a template for a new class of drug directed against all herpesviruses.
“We have found a new therapeutic target for herpesviruses,” he remarked. “We think it can be developed it into a new class of antiviral drugs to help overcome the problem of drug- resistant infections.”
Source: University of Utah School of Medicine; March 14, 2016.