Study Suggests Pleconaril Has Potential to Treat EV-D68 Infection

Investigators at Purdue University (West Lafayette, IN, USA) used advanced X-ray crystallography techniques to study the interaction between EV-D68 and the antiviral drug pleconaril. Pleconaril was developed in the 1990s but has not been approved by the [US] Food and Drug Administration primarily because of a side effect that puts women using birth control drugs at risk of conception.

Results published in the January 2, 2015, issue of the journal Science revealed that the hydrophobic drug-binding pocket in viral protein 1 contained density that was consistent with a fatty acid of about 10 carbon atoms. This density could be displaced by pleconaril. Further experiments showed that pleconaril inhibited EV-D68 at a half-maximal effective concentration of 430 nanomolar and might, therefore, be a possible drug candidate to alleviate EV-D68 outbreaks.

"The compound and the normal pocket factor compete with each other for binding into the pocket," said senior author Dr. Michael G. Rossmann, professor of biological sciences at Purdue University. "They are both hydrophobic, and they both like to get away from water by going into the pocket. But which of these is going to win depends on the pocket itself, the pocket factor, and properties of the antiviral compound."

Although pleconaril was found to be inactive against current strains of EV-D68, it was active against the original 1962 isolate. "Designing the best possible compound for these newer strains will take more time, but I hope that in a year or so we might have something," said Dr. Rossmann.

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