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12-07-2011 | Gastroenterology | Article

P7 inhibitors may suppress hepatitis C virus


Free abstract

MedWire News: Combining two different p7 inhibitors may result in the effective suppression of hepatitis C virus (HCV) replication and thus offer a potential multidrug treatment for patients with hepatitis C, study results indicate.

The findings arise from the observation of direct drug interactions with the HCV, as "current therapy comprising pegylated interferon (IFN) and ribavirin (Rib) is inadequate," explain the authors.

They add that this inadequacy, "combined with high cost and poor patient compliance, has driven the demand for new virus-specific drugs."

Stephen Griffin (University of Leeds, UK) and team used molecular modeling to assess the actions of two p7 inhibitors: adamantanes and alkylated imino sugars (IS). They found that these inhibitors attacked the HCV through separate mechanisms.

As resistance indicates antiviral effects, the team looked at the mechanisms by which resistance to both p7 inhibitors occurs. Adamantane resistance was found to be mediated by a L20F mutation, whereas IS resistance arose from a F25A polymorphism.

Griffin and team say that, as both inhibitors attack the HCV by different mechanisms, they are likely to work synergistically when used in combination.

"By learning how the HCV reacts to these molecules, we can design drugs that are likely to be more effective for longer," said Griffin.

He added: "We can also see how drugs could be used together with other 'direct-acting' drugs that target alternative viral targets, rather than individually or with IFN/Rib.

"In other words, a similar approach to treatment as that used for HIV."

HCV infection carries a high disease burden as it affects more than 3% of the world's population and leads to severe liver disease.

Finding effective treatment solutions are therefore of great importance, conclude the authors in the journal Hepatology.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Lauretta Ihonor

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