NIH has awarded Scripps Florida scientists just over $1 million for a three-year study to develop new high-throughput screening tests to find compounds that disable a protein essential to hepatitis C virus (HCV) replication.
Hepatitis C is a slow-progressing disease that causes inflammation of the liver and affects some 170 million people worldwide, according to the Hepatitis Foundation International. Like the current approach to HIV/AIDS, a cocktail-based therapeutic approach, which uses multiple inhibitors targeting distinct aspects of the HCV life cycle, has emerged as one of the most promising.
In the search for new treatments against HCV, it has become critical to develop novel targets to attack. Tellinghuisen’s new research is focused on a potentially potent, but somewhat neglected, enzyme. This protease—an enzyme that breaks down proteins—is known as NS2, which is necessary for productive infections that produce new viruses and spread the infection among cells. Timothy Tellinghuisen, a Scripps Florida associate professor, is the principal investigator for the study.
“The NS2 protein is needed for hepatitis C infections, but is poorly understood,” Tellinghuisen said. “The new grant will help us develop potential chemical tools to look at the role of NS2 in HCV biology because we really don’t know how the protein works.”
Some recent studies suggest that the NS2 protease may be involved in altering gene expression in the host cell and in helping the virus defend against apoptosis or programmed cell death, in addition to the more direct roles for the protein in viral replication and particle assembly.
Tellinghuisen and his colleagues have already developed a small-scale screen to identify compounds that disrupt viral replication through NS2 protease activity.
“Our overall goal is to turn our small-scale NS2 assay into an assay appropriate for high-throughput small-molecule screening,” he said, noting that would give the team access to the more expansive Molecular Libraries Probe Production Centers Network (MLPCN) screening center program at Scripps Florida.
MLPCN is a collaborative research network that uses use high-tech screening methods to identify small molecules to investigate the diverse functions of cells; Scripps Research is one of four large national centers.