Science Blog

I seem to have caught the flu. What can I do about it?
Dr Graeme Laver - former professor of biochemistry & molecular biology at the Australian National University
9 August 2007

Dr Graeme Laver is a former professor of biochemistry and molecular biology at the Australian National University in Canberra and was awarded the Australia Prize for excellence in the field of pharmaceutical design in 1996. Dr Laver proved the avian origin of human influenza, together with New Zealand’s Rob Webster, and his work led to the development of the antiviral drug Tamiflu. He has been a long time critic of the Federal Government’s plans to use the antiviral in the event of a bird flu pandemic.

You feel absolutely terrible. You have a throbbing headache, you are shivering with a high fever and there are horrible aches and pains in your legs and arms You are coughing a bit and your nose is all stuffed up. You have certainly caught the flu!

But as you lie there in utter misery, you are comforted by the thought that sooner or later you will start to get better. But what if you don’t, what if you get worse and go on to die? Thousands do, every year, and, sadly, not many seem to care. “Did you hear, Joe Smith died last week?” “Oh dear, what did he die from?” “Nothing serious, it was just a bout of the flu.”

Until recently, if you caught the flu, there was nothing you could do about it.

Now, suddenly, there are medicines available, if you take them soon after symptom onset, that will help you to recover and maybe save your life. One of these drugs is called Tamiflu and governments around the world have stockpiled Tamiflu in huge amounts to use in case a “bird flu” pandemic suddenly erupts. But Tamiflu is also very effective against "seasonal flu", the flu that comes along every winter, and it should be used by people who catch the flu, either because they have not been vaccinated, or because they experience vaccine failure.

Tamiflu was deliberately created by a process known as "rational drug design". Tamiflu and another flu drug, Relenza, were the very first anti-viral drugs to be developed using this method.

The tiny particles of the influenza virus have, on their surface, two proteins called haemagglutinin and neuraminidase. These are the proteins in influenza vaccines that are supposed to make you immune to the influenza virus.

Unfortunately, these proteins keep changing their structure all the time, so that if you take this year’s vaccine or you are infected by this year’s virus you may not have much protection against the changed virus that comes along next year. And if a ‘new’ virus (such as the deadly H5N1 "bird flu") comes along, you will have no protection whatsoever. That is very scary.

The protein on the flu virus, neuraminidase, is an enzyme that the virus uses when it wants to escape from an infected cell and spread in your body to infect other cells.
It was clear that if there was a drug that stopped the enzyme from working, there would be a “cure” for the flu.

Tamiflu is such a drug and this was created in the following way:

The neuraminidase protein was taken off flu virus particles and then crystallized. By passing an intense beam of X-rays through the crystal the exact shape of the neuraminidase molecule was discovered. This revealed the presence of a deep cleft, or canyon, on the enzyme that was the active catalytic site. Amazingly, this site had the same shape in all flu viruses, unlike the rest of the enzyme that differed in shape from strain to strain.

This meant that if a drug could be synthesized that bound tightly in the active site of the neuraminidase, a “plug drug”, that stopped the enzyme working, it would be effective against all flu viruses, even those, like the H5N1 “bird flu” virus, that have not yet appeared in man.

The first neuraminidase inhibitor, or plug drug to be deliberately created from a knowledge of the shape of the active site was called zanamivir or Relenza and was a very effective treatment for the flu. Relenza, however, is a powder that has to be puffed into the lungs, and many people find this unappealing. Another plug drug called oseltamivir or Tamiflu was then created that could be swallowed as a pill.

Tamiflu is most effective if taken soon after symptom onset. Six to 12 hours is ideal. 48 hours is almost too long. How can early treatment be achieved? One idea is to have Tamiflu available in the pharmacy where flu victims can get it quickly. In most countries, however, a doctor’s prescription has to be obtained first. Unfortunately the time taken to get a prescription is usually so long it means Tamiflu will no longer work.

There is no need for a prescription. If Tamiflu is dispensed for the wrong reason, to treat the common cold for example, where it will not work, nothing bad will happen, the influenza virus will not develop resistance, but the drug will be wasted and that should be avoided.

The solution is to have in the pharmacy a fast flu test so that people who think they have the flu can be tested on the spot, if positive be given Tamiflu right away and if negative be denied the drug.

This policy of “test-and-treat” should be implemented now throughout the world until it becomes firmly entrenched in influenza folklore.

Disclaimer: While Graeme has no financial gain from the sale of Tamiflu and Relenza, he does have shares in Biota Holdings who receive royalties from Relenza.

-------------

Comment

Return to main Science Blog page

If you are a scientist and wish to contribute to this Science Blog, please contact the AusSMC.
Comments received are moderated by the AusSMC and placement cannot be guaranteed.

The opinions expressed in this Science Blog are those of the authors, and do not necessarily represent the views of the Australian Science Media Centre.