Researchers from the University of California, Irvine, with assistance from the San Diego Supercomputer Center at UC San Diego, have found a new approach to the creation of customized therapies for virulent flu strains that resist current antiviral drugs.
The findings, published online this week in Nature Communications, could aid development of new drugs that exploit so-called flu protein 'pockets.'
Using powerful computer simulations on SDSC's new Trestles system, launched earlier this year under a $2.8 million National Science Foundation (NSF) award, UCI's Rommie Amaro and Robin Bush together with SDSC's Ross Walkercreated a method to predict how pocket structures on the surface of influenza proteins promoting viral replication can be identified as these proteins evolve, allowing for possible pharmaceutical exploitation.
"Our results can influence the development of new drugs taking advantage of this unique feature," said Amaro, an assistant professor of pharmaceutical sciences and computer science at UCI. Prior to joining UCI in 2009, Amaro was a postdoctoral fellow in chemistry at UC San Diego.
The search for effective flu drugs has always been hampered by the influenza virus itself, which mutates from strain to strain, making it difficult to target with a specific pharmaceutical approach. The most common clinical flu treatments are broad-based and only partially effective. They work by interrupting the action of an enzyme in the virus called neuraminidase, which plays a critical role in viral replication.
In 2006, scientists discovered that avian influenza neuraminidase (N1) exhibited a distinctive, pocket-shaped feature in the area pinpointed by clinically used drugs. They named it the 150-cavity.
Amaro and Bush, associate professor of ecology and evolutionary biology, conducted research using resources at the San Diego Supercomputer Center, as well as the National Institute for Computational S
|Contact: Jan Zverina|
University of California - San Diego