New approach found for customized flu strain therapies

University of California - Irvine researchers with assistance from the San Diego Supercomputer Center at UC San Diego have found a new approach to customized therapies to resistant virulent flu strains.
The findings could aid the development of new drugs that exploit so-called flu protein "pockets." Using the SDSC's new Trestles computer system, the researchers created a method to predict how pocket structures on the surface of influenza proteins promoting viral replication can be identified as the proteins evolve, allowing for the possibility of pharmaceutical exploitation, reports.
"Our results can influence the development of new drugs taking advantage of this unique feature," Rommie Amaro, an assistant professor of pharmaceutical sciences and computer science at UCI, said, according to
Effective flu drugs have been limited by the influenza virus itself, which mutates from strain to strain, making it difficult to target with a specific approach. In 2006, scientists discovered that avian influenza neuraminidase exhibited a unique, pocket-shaped feature in the area pinpointed by clinically used drugs. They called the pocket the 150-cavity.
Amaro and Robin Bush, an associate professor of ecology and evolutionary biology at UCI, created molecular simulations of flu proteins to predict how these structures move and change, as well as when and where the 150-cavity pockets will appear on the protein surface.
"Having additional antivirals in our treatment arsenal would be advantageous and potentially critical if a highly virulent strain, for example, H5N1, evolved to undergo rapid transmission among humans or if the already highly transmissible H1N1 pandemic virus was to develop resistance to existing antiviral drugs," Amaro said, reports.
Ross Walker, who runs the Walker Molecular Dynamics Lab at SCDC, developed a customized version of AMBER, a package of molecular simulation codes, to run the specific simulation.
"We initially used the Athena supercomputer at NICS, which provided us with all the initial comparison data before Trestles came online earlier this year," Walker, who is also an adjunct assistant professor in UC San Diego's Department of Chemistry and Biochemistry, said, according to "We had Trestles all ready to go as soon as the first H1N1 protein structure was available, and using the earlier work we did on Athena, we were able to put Trestles immediately to work to conduct simulations of the structure as part of this research."