New research yields possible solution to fighting EV-D68

New research conducted at Purdue University has found a class of compounds that may be effective in fighting infections caused by enterovirus D68.

The virus, which has stricken children with serious respiratory infections, might also be associated with polio-like symptoms in the United States and elsewhere.

The researchers have used a technique called X-ray crystallography to learn the exact build of the original strain of EV-D68 on its own and when bound to the anti-viral compound pleconaril. The research, which is still ongoing, has the potential to lead to the development of medications that inhibit infections caused by the virus.

A molecule called a pocket factor is located within the virus's protective shell, also called the capsid. When the virus binds to a human cell, the pocket factor is squeezed out of its pocket, which results in the destabilization of the virus particle. The particle then disintegrates and releases its genetic material to infect the cell and to replicate itself. Pleconaril binds into the pocket, blocking infection.

"The compound and the normal pocket factor compete with each other for binding into the pocket," Hanley Distinguished Professor of Biological Sciences at Purdue University Michael G. Rossmann said. "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 findings were recently published in Science, authored by Yue Liu, a graduate student; Ju Sheng, a technical assistant; Andrei Fokine, Geng Meng, Woong-Hee Shin, and Feng Long, post-doctoral research associates; Richard Kuhn, professor and head of Purdue's Department of Biological Sciences; Daisuke Kihara, a professor of biological sciences and computer science; and Rossmann.

"In this work, we only focused on the very original EV-D68 isolate, which was discovered in 1962," Liu said. "Strains in the current outbreaks have minor differences."

Although pleconaril is not active against current strains of EV-D68 tested thus far, it has been shown to be active against the original isolate. Further research, which will see small changes in the structure of pleconaril, may possibly lead to anti EV-D68 inhibitors against a broader spectrum of isolates.