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).

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