http://www.pnas.org/content/early/2016/03/09/1523686113
Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function
Significance
Epstein–Barr virus is a human herpesvirus associated with several types of malignancy. We show that spironolactone, a drug used to block mineralocorticoid activity, also has anti-EBV activity and that it acts by inhibiting the function of an essential EBV protein SM, which preferentially increases expression of specific EBV genes. We also show that the mineralocorticoid blocking activity is not the basis for spironolactone’s antiviral activity. Because the SM protein acts at steps of the viral life cycle distinct from those targeted by currently available therapies, this study paves the way for development of novel anti-EBV drugs to address emerging problems of drug resistance and toxicity.
Abstract
Clinically available drugs active against Epstein–Barr virus (EBV) and other human herpesviruses are limited to those targeting viral DNA replication. To identify compounds directed against other steps in the viral life cycle, we searched for drugs active against the EBV SM protein, which is essential for infectious virus production. SM has a highly gene-specific mode of action and preferentially enhances expression of several late lytic cycle EBV genes. Here we demonstrate that spironolactone, a mineralocorticoid receptor antagonist approved for clinical use, inhibits SM function and infectious EBV production. Expression of EBV viral capsid antigen is highly SM dependent, and spironolactone inhibits viral capsid antigen synthesis and capsid formation, blocking EBV virion production at a step subsequent to viral DNA replication. In addition, spironolactone inhibits expression of other SM-dependent genes necessary for infectious virion formation. We further demonstrate that molecules structurally related to spironolactone with similar antimineralocorticoid blocking activity do not inhibit EBV production. These findings pave the way for development of antiherpesvirus drugs with new mechanisms of action directed against SM and homologous essential proteins in other herpesviruses.
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Can anyone access the full paper to tell us what DOSE of spironolactone is needed to suppress EBV? BTW, I was on this med for years, as it is prescribed for hairy women (that's me!) to lessen hair growth. It was safe and easy to take. I stopped a few years ago and I have gone downhill, I think. So I will re-start it soon, I hope.
Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function
Significance
Epstein–Barr virus is a human herpesvirus associated with several types of malignancy. We show that spironolactone, a drug used to block mineralocorticoid activity, also has anti-EBV activity and that it acts by inhibiting the function of an essential EBV protein SM, which preferentially increases expression of specific EBV genes. We also show that the mineralocorticoid blocking activity is not the basis for spironolactone’s antiviral activity. Because the SM protein acts at steps of the viral life cycle distinct from those targeted by currently available therapies, this study paves the way for development of novel anti-EBV drugs to address emerging problems of drug resistance and toxicity.
Abstract
Clinically available drugs active against Epstein–Barr virus (EBV) and other human herpesviruses are limited to those targeting viral DNA replication. To identify compounds directed against other steps in the viral life cycle, we searched for drugs active against the EBV SM protein, which is essential for infectious virus production. SM has a highly gene-specific mode of action and preferentially enhances expression of several late lytic cycle EBV genes. Here we demonstrate that spironolactone, a mineralocorticoid receptor antagonist approved for clinical use, inhibits SM function and infectious EBV production. Expression of EBV viral capsid antigen is highly SM dependent, and spironolactone inhibits viral capsid antigen synthesis and capsid formation, blocking EBV virion production at a step subsequent to viral DNA replication. In addition, spironolactone inhibits expression of other SM-dependent genes necessary for infectious virion formation. We further demonstrate that molecules structurally related to spironolactone with similar antimineralocorticoid blocking activity do not inhibit EBV production. These findings pave the way for development of antiherpesvirus drugs with new mechanisms of action directed against SM and homologous essential proteins in other herpesviruses.
* * *
Can anyone access the full paper to tell us what DOSE of spironolactone is needed to suppress EBV? BTW, I was on this med for years, as it is prescribed for hairy women (that's me!) to lessen hair growth. It was safe and easy to take. I stopped a few years ago and I have gone downhill, I think. So I will re-start it soon, I hope.