A research team from Purdue University in Indiana have made a breakthrough in learning about the virus, Enterovirus D68 (EV-D68) and the potential development of drugs that inhibit infections caused by the most recent strains of the virus.
The research was published in the journal Science on Friday.
The researchers have used a technique called X-ray crystallography to learn the precise structure of the original strain of EV-D68 on its own and when bound to an anti-viral compound called “pleconaril.”
A molecule called a “pocket factor” is located within a pocket of the virus’s protective shell, called the capsid. When the virus binds to a human cell, the pocket factor is squeezed out of its pocket, resulting in the destabilization of the virus particle, which then disintegrates and releases its genetic material to infect the cell and to replicate itself.
The antiviral compound pleconaril also binds into the pocket, inhibiting infection.
Michael G. Rossmann, Hanley Distinguished Professor of Biological Sciences at Purdue University and lead researcher said, “The compound and the normal pocket factor compete with each other for binding into the pocket. 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.”
Purdue graduate student and one of the authors of the paper, Yue Liu says, “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 is active against the original isolate. Small changes in the structure of pleconaril are likely to lead to anti EV-D68 inhibitors against a broader spectrum of isolates.
Purdue researchers became interested in studying pleconaril’s potential effectiveness against EV-D68 after an outbreak of about 20 cases of acute flaccid paralysis was reported in California between 2012 and 2014. Out of those cases, two tested positive for EV-D68.
“This suggests the potential association of EV-D68 with polio-like illness,” Liu said.
From mid-August to December 18, 2014, CDC or state public health laboratories have confirmed a total of 1,152 people in 49 states and the District of Columbia with respiratory illness caused by EV-D68.
From August 2 to December 18, CDC has verified reports of 102 children in 34 states who developed acute flaccid myelitis that meets CDC’s case definition.
Watch video interview with Rossmann and Liu below: