Virus find reinforces Biotron's 'exit strategy'

Directors of Canberra-based HIV drug-therapeutic company Biotron have announced that the company's researchers have confirmed that two Australian native viruses -- Ross River Virus, the agent of epidemic polyarthritis, and its cousin, Barmah Forest Virus -- possess genes for ion channels.

The discovery, published last week in the prestigious Journal of Biological Chemistry, is likely to set virologists' antennae waving again.

Biotron had previously surprised sceptical virologists by showing that the Vpu gene in Human Immunodeficiency Virus (HIV), the world's most intensively studied virus, encodes an ion channel - and Biotron's synthetic molecule BIT009 blocks the channel, preventing the virus replicating.

All higher life forms, including animals, plants and fungi, have a diverse array of ion-channel genes. They encode tiny molecular valves that regulate the two-way flow of charged atoms -- ions, like sodium, calcium and potassium -- through cell membranes.

Because ion channels regulate flux of elements that are essential for normal cellular metabolism and activity, they're fundamental to life itself.

Viruses aren't alive, so researchers must now explain why some, perhaps many, viruses carry around do-it-yourself ion channel genes.

One of the researchers involved in the Biotron project, Prof Peter Gage, of the John Curtin School of Medical Research at the Australian National University, said that, "Nature makes nothing that is useless in a virus. There are no degrees of freedom in something so basic."

Biotron's Virion project aims to develop new anti-HIV therapeutics that will disrupt the virus' replication by jamming its Vpu ion channel.

Biotron's BIT009 appears to inhibit replication of HIV, apparently by jamming the Vpu ion channel, somehow preventing new virus particles, or virions, 'budding' from the surface of infected white blood cells. The company is preparing to take BIT009 into Phase I trials in the first half of next year. Biotron's MD, Dr Michelle Miller, said Biotron's researchers had now confirmed predictions that the so-called 6K proteins of Ross River and Barmah Forest viruses, both alphaviruses, were also ion channels. The discovery could open up new options for the treatment of these and other viral diseases.

Miller said the M2 strain of the influenza virus also harboured an ion-channel gene, and Biotron had learned that an overseas research team had now identified an ion-channel gene in the Hepatitis C virus. The discovery has not yet been published.

Gage said that, "There are no therapies for hepatitis C, and it's potentially lethal, so it could be a target for a channel-blocking therapeutic." None of the existing AIDS drug target the 'budding' process from the host cell's membrane. What might be called "exit strategy" anti-virals would prevent viral infections spreading inside the body by locking virions inside infected cells.

This approach has already been exploited -- although via a different mechanism -- in the anti-influenza compound Relenza, developed by Melbourne-based Biota Holdings and Glaxo-Wellcome.