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Updated: Mar 24, 2026

Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Spironolactone blocks Epstein-Barr virus production by inhibiting EBV SM protein function
Dinesh Verma1, Jacob Thompson1, Sankar Swaminathan2
1Division of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132.
None:
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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