CSIRO’s expertise in determining protein structure, and therapeutic design led to the development of Relenza™, the first drug successful in treating the flu.
Background
Influenza, the flu, affects as many as 500 million people each year. The economic impact is substantial in terms of days off work and productivity lost each year. In high-risk groups complications of influenza such as pneumonia can be fatal. These groups include:
In a typical Australian winter, around 1 500 deaths are attributed to the virus.
The flu virus mutates rapidly. Humans suffer repeat infections as the immunity we develop to one infection does not protect us from subsequent mutant viruses.
Disabling the flu virus
CSIRO, in collaboration with research partners and industry, has revolutionised the treatment of influenza with drugs of pinpoint precision.
Using X-ray crystallography, researchers have found a region on one of the surface proteins of the flu virus that does not change in any of its strains.
Using the methods of rational drug design we have designed a drug that 'locks' onto this section of the virus and stops the infection progressing. This approach is now also being used for:
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diabetes
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hepatitis
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cancer.
Crystal structure
This research began in 1978 when Dr Graeme Laver of the Australian National University's John Curtin School of Medical Research, in Canberra, obtained crystals of one of the crucial surface virus proteins (neuraminidase) for the first time.
Next CSIRO's Dr Peter Colman and Dr Jose Varghese produced improved crystals and solved the three dimensional structure of two influenza neuraminidases with X-ray crystallography. They used amino acid sequence data generated by Dr Colin Ward and his CSIRO colleagues to build the three-dimensional (3D) structure from their X-ray crystallography data.
With this information they identified and characterised a small unchanging region in the neuraminidase protein that occurs in all strains of influenza. This showed a chink in the virus' armour.
Designing Relenza™
In a typical Australian winter, around 1 500 deaths are attributed to the influenza virus.
A group of scientists led by Professor Mark von Itzstein at the Victorian College of Pharmacy (VCP), Monash University, Melbourne, designed and synthesised a special drug that 'locks' onto this section of the virus and prevents it from spreading in the infected patient. In this way the infection is halted.
This collaborative research between CSIRO and VCP was funded by the Melbourne-based biotechnology company Biota Holdings Ltd. Biota was floated on the Australian stock exchange to raise funds to conduct this project.
Dr Colman, Professor von Itzstein and Dr Laver shared the 1996 Australia Prize for their contributions to this project.
Relenza™ goes to market
Clinical trials conducted by Glaxo Wellcome in Australia and overseas have shown that Relenza™ significantly reduces the duration and severity of flu symptoms, especially if it is taken soon after a person is infected.
Recently CSIRO scientist Dr Jenny McKimm-Breschkin has tested the ability of Relenza™ to inhibit the H5N1 influenza virus, or bird flu. Governments are planning to stockpile flu drugs including Relenza™ as protection against future pandemics such as the H5N1 bird flu.
The same successful approach to drug design that led to the development of Relenza™ is continuing in CSIRO.
Learn more about CSIRO's work in Health & Wellbeing.
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