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Scripps research team identifies key molecules that inhibit viral production
Date:3/10/2009

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.

The core protein is particularly important in the assembly of the hepatitis C nucleocapsid, an essential step in the formation of infectious viral particles; the nucleocapsid is the viral genome protected by a protein coat the capsid. This core protein plays an essential role in the HCV cycle during assembly and release of the infectious virus, as well as disassembly of viral particles upon entering host cells.

Looking closely at the core interaction with itself, Strosberg developed several novel quantitative assays or tests for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production.

"People have been dreaming about inhibiting protein-protein interactions, as a new El Dorado for finding novel drug targets," says Strosberg, "but few conclusive studies have emerged, except in the virus-host area."

Inhibition of HCV Production

The new research, however, led to the discovery of two peptides that inhibited HCV production by 68 percent and 63 percent, respectively; a third related peptide showed 50 percent inhibition. When added to HCV-infected cells, e
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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