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Pleconaril may be effective treatment for EV-D68
Due to considerable structural similarities to well-known human rhinoviruses, enterovirus D68 could also be effectively treated with pleconaril, according to study findings in Science.
Michael G. Rossmann, MSc, PhD, of Purdue University, and colleagues used X-ray crystallography to evaluate the specific structure of the original strain of EV-D68 alone and when interacting with pleconaril (Picovirl, Schering-Plough).
Michael G. Rossmann
“In this work we only focused on the very original EV-D68 isolate, which was discovered in 1962,” study researcher Yue Liu said in a press release. “Strains in the current outbreak have minor differences.”
Researchers found that the structure of EV-D68 was similar to that of human rhinoviruses, for which pleconaril was originally designed.
When a virus binds to a human cell, a molecule called a “pocket factor” is forced out of its pocket, destabilizing the virus particle, which disintegrates and releases its genetic material to infect the human cell.
“The compound and the normal pocket factor compete with each other for binding into the pocket,” Rossmann said in the release. “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.”
The antiviral compound replaced the pocket factor and inhibited infection, according to researchers, indicating pleconaril was active against the original EV-D68 isolate.
“Furthermore, sequence alignment of 188 EV-D68 strains found between 1962 and 2013 indicates that residues in VP1 that interact with pleconaril, as identified from the complex structure, are completely conserved, with one exception,” Rossmann and colleagues wrote. “Therefore, pleconaril is likely to inhibit not only the prototype strain examined here but also many other strains.”
Disclosure: The study was supported by NIH. The researchers report no relevant financial disclosures.
