The research, led by Professor Donny Strosberg of Scripps Florida, was published on March 4, 2009, in the Journal of General Virology's advance, online edition, Papers in Press.
In the new study, Strosberg and his colleagues describe peptides (molecules of two or more amino acids) derived from the core protein of hepatitis C. The team found that these peptides inhibit not only dimerization of the core protein (the joining of two identical subunits), but also production of the actual virus itself.
"We went for the simplest solution, taking a peptide from core to see if we could block the interaction," Strosberg said, "and it did."
The Problem with Hepatitis C
With over 170 million people infected worldwide by HCV, new therapeutic strategies for HVC-a blood-borne disease that affects the liver-are urgently needed.
But one of the critical problems in developing drugs for HCV is that it mutates at such prodigious rates. An RNA virus like hepatitis C can mutate at a rate estimated as high as one million times that of DNA viruses; in contrast, DNA viruses contain an enzyme (polymerase) that acts as something of a proof reader to ensure that newly transcribed DNA strands are the same as the original, helping to reduce mutations.
"In one sense, the ongoing issue with hepatitis C is that there are still so very few drugs to treat the virus and very few tools to study it," Strosberg said. "We set out to develop new tools and to identify a new target - core, the capsid protein. By targeting the interactions of core with itself or other proteins, we could reduce the problem of rapid mutation not only because the core protein mutates significantly less, but also because mutations that would affect the interface between core and itself or other proteins would often be more likely to deactivate the virus, in contrast to mutations in viral enzymes which often lead to increased resistance to drugs."
Recent efforts to develop therapeutic strategies against HCV have concentrated on designing inhibitors that target several of the 10 HCV proteins that comprise the virus, including mostly the non-structural proteins. However, as the study points out, the one HCV structural protein that has not been targeted yet is the core protein, the one responsible for assembly and packaging of the HCV RNA genome.
The Core of the Matter
Core, the most conserved protein among all HCV genotypes, plays several essential roles in the viral cycle in the host cell; studies have suggested that these core-core or core-other protein interactions can modulate various functions including signaling, apoptosis or programmed cell death, lipid metabolism, and gene transcription.