A Heat Shock Protein Inhibitor Prevents Hepatitis C Infection

A potential treatment for hepatitis C virus (HCV) infection is based on a naturally occurring plant bioflavonoid that inhibits the action of the two heat shock proteins HSP40 and HSP70.

Investigators at the University of California, Los Angeles (USA) were studying the cellular proteins that interact with HCV nonstructural protein 5A (NS5A), one of the proteins that has been implicated in regulation of viral genome replication. Among other tools, they used mass spectrometric analysis, confocal microscopy, and Western blot analysis of co-immunoprecipitated NS5A complexes from cell extracts to search for proteins that interacted with NS5A.

They reported in the December 2009 issue of the journal Hepatology that these analytical techniques identified two heat shock proteins, HSP40 and HSP70, as critically linked to NS5A. The importance of these proteins to viral replication was confirmed in an experiment 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.

"Quercetin may allow for the dissection of the viral life cycle and has potential therapeutic use to reduce virus production with low associated toxicity," said senior author Dr. Samuel French, assistant professor of pathology at the University of California, Los Angeles. "Because Quercetin targets cellular proteins rather than viral proteins, there is less likelihood of developing viral resistance. Cellular proteins cannot change like viral proteins can."

"This is an important finding because we can block these proteins with the idea of reducing the level of the virus in people and, ideally, completely eliminate it," said Dr. French.

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