January 6, 2012

Enzyme structure opens doors to new treatments of viruses including HIV and Hep C


By Darren Quick

20:28 January 5, 2012

Viruses can enter the body via a number of pathways and while scientists have known how to block the main one used by viruses such as HIV, Hepatitis C, Dengue Fever and West Nile virus for some time, these viruses are able to bypass this main pathway to replicate and cause disease via a second pathway by hijacking an enzyme known as endomannosidase. Now an international team of researchers has determined the three-dimensional structure of the enzyme endomannosidase, opening the door for new treatments to a variety of deadly viruses through the development of inhibitors that block this bypass route.

The international team, led by Associate Professor Spencer Williams from the University of Melbourne's Bio21 Institute and Professor Gideon Davies from the University of York in the UK, studied bacterial endomannosidase as a model for the same human enzyme.

"If we understand how the viruses use our enzymes, we can develop inhibitors that block the pathway they require, opening the door to drug developments," said Professor Davies, of the Department of Chemistry at York. "It was already known how to block the main pathway for these viruses but until now, this endomannosidase bypass pathway has proved a considerable challenge to study."

Using synchrotron technology, the team successfully determined the three-dimensional structure of the enzyme, thus revealing details on how viruses essentially play biological "piggy-back" to turn our own cellular machinery to their own nefarious purposes.

Associate Professor Williams also told Australia's ABC News that, because the findings relate to our own pathways, which aren't prone to mutation, rather than on viral pathways, which are, the risk of creating drug-resistant viral strains is also reduced. The team also hopes that their work will have applications beyond viruses and will lead to similar treatments for other diseases including cancer.

While the research will provide hope for the development of drugs to combat these deadly viruses that infect more than 180 million people worldwide each year, Associate Professor Williams expects it will take at least 10 years to develop such virus-fighting drugs based on the research.

The team's study is published as an open access article in the journal, Proceedings of the National Academy of Sciences (PNAS).


New study explains why hepatitis C virus is difficult to eliminate


Updated: 2012-01-05 16:56:58 CST

Individuals who have received a positive lab test for hepatitis C have a very high risk of experiencing liver problems, as there is currently no cure for the condition. However, a new study out of the University of North Carolina at Chapel Hill may help explain why the infection is so difficult to eliminate and points to the possibility of a new treatment .

The researchers found that the hepatitis C virus binds to a segment of genetic material in liver cells called microRNA-122. The molecule plays a role in regulating the reproduction of normal liver cells. When the virus attaches itself to this bit of genetic material, it is able to utilize it for the same purposes, ensuring consistent reproduction of the virus.

Findings from the investigation may play a role in the development of new medications that make it more difficult for the virus to replicate itself. The researchers said there is already an experimental drug in development that binds to microRNA-122, thereby preventing the virus from using it for its own purposes.
Given the high rates of the disease and significant burden of liver problems among those infected, the new medication could represent a major advance.


HCV Antivirals Cost-Effective for Injecting Drug Users


Last Updated: January 06, 2012.

Antivirals are cost-effective for injecting drug users where the chronic prevalence of hepatitis C virus infection is less than 60 percent, according to a study published in the January issue of Hepatology.

FRIDAY, Jan. 6 (HealthDay News) -- Antivirals are cost-effective for injecting drug users (IDUs) where the chronic prevalence of hepatitis C virus (HCV) infection is less than 60 percent, according to a study published in the January issue of Hepatology.

Natasha K. Martin, D.Phil., of the University of Bristol in the United Kingdom, and colleagues compared the cost-effectiveness of providing antiviral treatment for IDUs, ex or non-IDUs, or no treatment. They developed a model of HCV transmission and disease progression which incorporated assumptions including: a specified number of antiviral treatments to be given at the mild HCV stage over a period of 10 years, no retreatment for those who failed treatment, potential reinfection, and scenarios for baseline IDU HCV chronic prevalence of 20, 40, and 60 percent. Long-term costs and outcomes measured in quality adjusted life years (QALYs) were performed and the incremental cost-effectiveness ratio (ICER) was compared for no treatment, antiviral treatment for IDUs, and antiviral treatment for ex/non-IDUs.

The researchers found that, in the 20 and 40 percent baseline chronic prevalence settings, antiviral treatment for IDUs is the most cost-effective option compared with no treatment (ICER, £521 and £2,539 per QALY saved, respectively). Treatment of ex/non-IDUs dominated here. Treating ex/non-IDUs was slightly more likely to be cost-effective at a baseline chronic prevalence of 60 percent, and treating IDUs dominated due to high reinfection.

"Treating chronic HCV infection among injectors and ex- or noninjectors is cost-effective, but treating injectors may be more cost-effective when the chronic HCV prevalence among IDU is below 60 percent," the authors write.

Two of the study authors disclosed financial ties to the pharmaceutical industry.

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