Hep B mutation analysis platform developed by Vic disease lab

By Melissa Trudinger
Thursday, 16 September, 2004

The Victorian Infectious Diseases Reference Laboratory (VIDRL) has developed a platform which analyses mutations in hepatitis B virus strains carried by patients with chronic disease, and then recommends treatments based on the virus resistance profile.

The system, developed by VIDRL in collaboration with the Victorian Partnership for Advanced Computing (VPAC), can be used as a management tool for infected patients.

VIDRL director Dr Stephen Locarnini said the system was initially developed about five years ago as a genomic analysis engine and database used to classify HBV strains, and catalogue the mutations, with a link to patient data such as treatment history.

"We realised we could develop an individualised antiviral drug resistance management tool," he said. "Through VPAC we have been able to extend a simple database into a more sophisticated tool."

Using related enzymes from HIV as a model, the molecular structure of the HBV polymerase was modelled, and mutations mapped, providing understanding of the evolution and mechanisms of resistance. Because the database is linked to patient treatment histories, the effect of each therapeutic treatment can be tracked to provide information on how resistance develops.

"The model is providing unique insights into how the virus evolves when we use different therapies," Locarnini said. "We're now looking at whether we can use the model to predict the best therapy to use to treat the patient."

The database now has more than data from more than 1000 patients, including some 40,000 mutations in envelope proteins. In addition to making the database freely available to other HBV clinical researchers online, VIDRL researchers used the same approach last year to rapidly generate models of key SARS virus enzymes, and Locarnini said it would be readily applicable to other viruses too.

"We're now using it to look at mechanisms of inhibition and resistance, and rational drug design," he said. "Modelling takes it to a new level, clearly there is some IP potential. We're just starting to learn about developing collaborations and strategic alliances."

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