Investigators at the University of California, Los Angeles (USA) had been studying the relationship between the viral nonstructural protein 5A (NS5A) and the host heat shock proteins HSP40 and HSP70, an interaction necessary for successful HCV infection. The importance of the heat shock proteins to viral replication had been established in a study where tissue cultures were treated with the heat shock protein inhibitor Quercetin, a naturally occurring plant bioflavonoid. This treatment significantly reduced HCV invasion of the tissue culture cells.
In the current study, which was published in the January 30, 2012, online edition of the journal Hepatology, the investigators isolated a chain of amino acids from the C-terminal end of the NS5A protein. Deletion of this peptide prevented formation of the critical NS5A-heat shock protein complex. Addition of the peptide to other segments of NS5A restored its ability to form the complex. When the C-34 peptide was used to compete with the intact virus, the peptide significantly reduced intracellular viral protein levels, in contrast to same-size control peptides from other NS5A domains.
“This is important because we have developed a small peptide that binds to that site and blocks the interaction between the proteins that is important for viral replication,” said senior author Dr. Samuel French, assistant professor of pathology at the University of California, Los Angeles. “This is another, potentially highly efficacious way to block replication of hepatitis C. We were surprised that this peptide works this well. While its mechanism is different, the activity of this peptide is comparable to other newly developed antivirals.”
“There is no direct pressure on the virus, so it is less likely to mutate and develop resistance,” said Dr. French. “The goal is to achieve a sustained response, essentially a cure, meaning there is no more virus replication. There are a lot of drugs coming out now that are designed to stop hepatitis C replication, but resistance is still an issue. About 10% to 20% of patients on the new drugs become resistant. This new peptide may help combat resistance.”
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