Research findings point toward a class of compounds that could be effective in combating infections caused by enterovirus D68.
This has stricken children with serious respiratory infections and might be associated with polio-like symptoms in the United States and elsewhere.
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.
The researchers are working with the Centers for Disease Control and Prevention and are studying these newer strains to determine their structures.
"The need for an effective antiviral agent for treatment of EV-D68 infections was made apparent by the widespread and large numbers of EV-D68 infections (in 2014), many of which were associated with significant morbidity," said Mark A. McKinlay, director of the Center for Vaccine Equity at the Task Force for Global Health.
"The determination of the structure of the EV-D68 reported here by Michael Rossmann and his team represents an important step in this direction. The strain of EV-D68 used in the study is from 1962, and Michael's team along with Steve Oberste's group at CDC have shown that this strain is inhibited by pleconaril at clinically achievable concentrations. Testing of pleconaril against the current circulating strains at CDC thus far showed these strains are not susceptible to the antiviral compound."
McKinlay, who collaborates with the CDC on polio eradication efforts, has been a key figure in pharmaceutical-company collaborations with Rossmann's group to discover and develop pleconaril.
Once the newer strains are better understood, the ongoing research could yield compounds that are effective against these strains.
"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," Rossmann said.
Rossmann and Kuhn as well as David Stuart's team in Oxford, England, working with Zihe Rao's group in Beijing were among the first scientists to reveal important details of the structure of enterovirus 71, or EV71, which causes hand, foot and mouth disease, and is common throughout the world. Although that disease usually is not fatal, the virus has been reported to cause fatal encephalitis in infants and young children, primarily in the Asia-Pacific region.
Rossmann's and Kuhn's collaborative research has looked at virus structures in complex with receptors that permit entry of the virus into cells, and inhibitors of virus replication for a variety of viruses.
Like EV-D68 and EV71, poliovirus is an enterovirus and is within the large family called picornaviruses. Non-polio enteroviruses are common viruses and cause about 10 to 15 million infections in the United States each year, but most infected individuals have only mild illness, similar to a common cold, according to the CDC.