Will New Drugs Stop Hepatitis C Virus in its Tracks?

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http://www.infectioncontroltoday.com/news/2011/06/will-new-drugs-stop-hepatitis-\

c-virus-in-its-tracks.aspx Will New Drugs Stop Hepatitis C Virus in its Tracks?

Targeted multi-drug treatments for hepatitis C patients that could stop the

virus in its tracks have come a step closer, thanks to researchers at the

University of Leeds, UK.

The study by Dr and colleagues, published in the journal

Hepatology, reveals how two prototype small molecule drugs, known as p7

inhibitors, can each attack different parts of the hepatitis C virus. Their

findings suggest that p7 inhibitors could be a powerful way of suppressing

hepatitis C, when used together with the latest generation of 'direct-acting'

drugs.

More than 170 million people -- or 3 percent of the world's population -- are

infected with the hepatitis C virus. The virus causes severe liver disease and

is a leading cause of liver-related deaths, organ transplants and liver cancer.

At the moment, patients are typically treated with PEGylated interferon alpha

(IFN) and ribavirin (Rib) - drugs that work by boosting the patient's immune

system. However, the effects of these drugs can depend on the individual

patient's genetic make-up. To make matters worse, hepatitis C is often resistant

to the therapy and fails to suppress the virus for long enough. The treatment is

also expensive and can trigger unpleasant side effects. Many patients stop

taking the drugs or do not take them when they should.

To address this, researchers are looking at new classes of drugs that work in

a different way to either IFN or Rib and target the virus directly. The aim is

to find groups of these 'direct-acting' drugs that each attack a different

target, making it much, much harder for the virus to fight back.

University of Leeds researchers are focusing on drugs that target the p7 ion

channel - a protein made by hepatitis C that allows the virus to continue

spreading. In previous studies, Dr and colleagues worked out how the p7

ion channel could be blocked by certain types of small molecule, stopping the

hepatitis C virus in its tracks. Their latest work looks at two particular

classes of p7 inhibitor - adamantanes and alkylated imino-sugars – and confirms

that these molecules do, indeed, attack their intended target through separate

mechanisms.

The researchers used a combination of molecular modelling and lab-based

experiments to study the drugs' interaction with hepatitis C. Importantly they

observed how the virus responded to the two types of drug and determined that

each of these responses was very different. This suggests that the drugs would

work well in combination, tackling the virus on a number of fronts.

Lead author, researcher Dr , from the University of Leeds'

School of Medicine, said: " Hepatitis C has always been an extremely difficult

condition to treat effectively because the virus evolves so quickly and develops

resistance to drugs that are used to treat it. This new class of small molecule

drugs, the p7 inhibitors, attack the virus directly. As we have discovered here,

they each do so in quite a different way which allows us to combine their

effects.

" By learning how the hepatitis C virus reacts to these molecules, we can

design drugs that are likely to be more effective for longer. We can also see

how such 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. "

The study was conducted in collaboration with Professor Mark

(University of Leeds, Faculty of Biological Sciences), Professor Colin Fishwick

and Dr (University of Leeds, School of Chemistry) and Professor

Weinman (University of Kansas).

The work was funded by the UK Medical Research Council, Yorkshire Cancer

Research and the University of Leeds Biomedical and Health Research Centre.