Researchers Eye This Older Drug to Inhibit CMV

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The researchers screened a library of 1,280 such pharmacologically-active compounds to see if any of these might inhibit CMV replication in laboratory cell cultures.
The researchers screened a library of 1,280 such pharmacologically-active compounds to see if any of these might inhibit CMV replication in laboratory cell cultures.

Emetine, a drug that was used in the past to treat amebiasis before other drugs took its place decades ago, may inhibit cytomegalovirus (CMV), a herpesvirus that can cause serious disease in immunocompromised individuals, including those with HIV or organ transplant recipients, according to a study published in PLOS Pathogens.

Ravit Boger, MD, associate professor of pediatrics and oncology at the Johns Hopkins University School of Medicine, and colleagues partnered with the National Institiutes of Health and searched for useful drugs by screening those already approved by the US Food and Drug Administration for new uses. The researchers screened a library of 1,280 such pharmacologically-active compounds to see if any of these might inhibit CMV replication in laboratory cell cultures.

Results from the study showed that much lower concentrations of emetine can inhibit CMV as compared to those used for amebiasis, and less frequent doses might be effective for CMV inhibition. Indeed, tests in infected cells in the laboratory and in live mice showed that very low doses of emetine significantly reduced viral replication in both of these models (75 nanomolar in test tube and 0.1 milligram per kilogram in mice). Additionally, with a long half-life of 35 hours, the drug exerted its effects over a sustained period, effectively inhibiting virus replication at 14 days after three doses.

Additional investigation revealed that emetine's action against the virus was due to its effects on cellular proteins that control the cell cycle. 

Dr Boger cautioned in a prepared statement that researchers still have a long way to go before emetine or similar agents that target protein interactions in the cell can be considered for treatment of CMV. No one yet knows what an effective low dose would be, what short- and long-term side effects might occur, and whether the drug would be safe for this use. However, old data from higher doses used for amebiasis are encouraging.

“But if further research affirms its potential value,” she said, “emetine might eventually be used in patients who don't respond to approved anti-CMV drugs, alone or in combination with these.” Additionally, she says, developing a better understanding of emetine's activity in cells could lead to discovery of new drugs that take advantage of the same or similar pathways.

Funding for this study came from the National Center for Advancing Translational Sciences. 

Reference

1. Mukhopadhyay R, Roy S, Venkatadri R, et al.  Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus. PLOS Pathogens. 2016; http://dx.doi.org/10.1371/journal.ppat.1005717

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