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Spread of bird flu to humans only “matter of time

Spread of bird flu to humans only “matter of time”

An Australian expert on the flu virus has warned that it is only a matter of time that one of the present strains of bird flu will jump species and be spread from human to human.

However, Dr Jose Varghese, Chief Research Scientist of the Division of Molecular and Health Technologies at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Melbourne, says both New Zealand and Australia are well-prepared to handle any outbreak.

Dr Varghese, who was visiting the national Centre for Molecular Biodiscovery, hosted by The University of Auckland, said all global flu pandemics had avian origins.

“We are worried of course that the virulent avian strain that has been killing people recently will eventually become ‘humanised’ and jump the species. I guess it’s just a matter of when, not if.

“The current theory is that farm animals, typically pigs, become infected with both an avian and a human flu strain at the same time. The two viruses exchange genes in the animal host and produce a human adapted virus.”

Dr Varghese determined the structure of a surface enzyme (neuraminidase) of the influenza virus with a CSIRO colleague, Dr Peter Coleman, in 1983, leading to the development of a new class of anti-viral drugs in the late 1990s which are potent inhibitors of the enzyme.

The first of these, the drug, Relenza ™ was developed by CSIRO and Biota Holdings Ltd using structure-based drug design methods, based on the three dimensional atomic structure of neuraminidase. The drug was then taken to clinical trials by Glaxo Pharmaceuticals.

The drug Tamiflu ™ was developed later in the United States based on the structural work of the CSIRO group and the lead compounds subsequently identified for new drug development.

Both drugs target a small “pocket” in the surface enzyme, neuraminidase, which is identical in every strain of influenza, making them effective against all strains and sub-types of influenza irrespective of their origin.

These drugs can also be used prophylactically to prevent the spread of infection if used early in an outbreak. As both drugs act as a molecular “plug” which prevents the virus replicating, they also shorten the duration of the illness, enabling more effective management and treatment.

Dr Varghese says because the flu virus can mutate rapidly, flu vaccines are only effective against known strains of influenza and cannot deal effectively with emerging strains, particularly those that arise during global pandemics.

“The fact that we now have these anti-viral drugs that work against whatever strain of flu is around is a big bonus. We also learnt a lot from the SARS epidemic – that if we get to the places where an infection is breaking out and contain it quickly, we are able to control these diseases.”

The possibility of emerging drug resistance to the neuraminidase inhibitors is being closely monitored by the CSIRO, says Dr Varghese.

“We‘re finding very little drug resistance at present, but we are watching what we consider may be a weak link in Tamiflu ™. Unlike Relenza ™, to work, Tamiflu ™ depends on the viral neuraminidase itself making an internal change. This provides an opportunity for the influenza virus to mutate to stop that happening.”

Dr Varghese says the methodology which led to the design of the anti-viral neuraminidase inhibitors has huge potential for new drug development and technologies to combat other infectious diseases, and major killers such as cancer, heart disease and diabetes.

“Structural biology – that is our understanding of how proteins work at a molecular level – has revolutionised biology. It is a discipline that has grown exponentially in the last 20 years and will make a huge contribution to medical science this century.

“By understanding protein structures and how processes work at a molecular level, we can manipulate and modulate biological systems and avoid the hit and miss approach we have used in the past to develop new drugs.”

Structure-based drug design, says Dr Varghese, overcomes the lack of specificity of drugs developed by traditional, high through-put, chemical screening.

“One of the problems with the traditional approach is that we know certain compounds inhibit certain functions, but we don’t know if other processes in the body are being affected. The benefit of structure-based drug design is that we can design a drug, like these anti-viral drugs, that is exquisitely selective.”

The Centre for Molecular Biodiscovery is one of seven national centres of research excellence established by the Government in 2002 to drive new drug development and technologies to combat major diseases in New Zealand. It is taking a leading role in post-genomic science by merging traditional scientific disciplines to improve human health.


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