Chink in the armour of H5N1 bird flu virus

Aug 20 2006

British scientists say they have made a breakthrough in their development of a bird flu drug that could treat humans in the event of an outbreak.

However they warn that it could be another five years before a final version of the drug is ready to be used to treat the H5N1 virus.

At present the H5N1 strain of bird flu remains a disease predominantly of birds and all of the 239 cases of human infection to date, have been from direct contact with infected birds.

Though scientists insist there is as yet no evidence the virus is mutating, which would enable it to transfer between humans, there is concern this could happen.

As many as 60 percent of those infected have died, and the best known drugs to tackle H5N1 infection in humans are oseltamivir known as Tamiflu and zanamivir known as Relenza, both of which were originally developed to fight other forms of human flu.

A team of scientists led by John Skehel of London's National Institute of Medical Research say they have found a chink in the armour of the H5N1 virus that could lead to more potent drugs against the deadly virus.

The H5N1 virus spreading around the globe has a surface protein which helps the virus penetrate and infect cells.

This protein is called neuraminidase, the N1 in H5N1 and is the enzyme targeted by the drugs Tamiflu and Relenza, which are being stockpiled by some countries in case the H5N1 bird flu becomes a human pandemic.

However these drugs were designed on the basis of the atomic structures for two other forms of neuraminidase in other strains of flu, the only two seen so far through x-ray microscopes, and no one knows how well these antivirals would perform against the N1 protein if H5N1 begins to spread easily among people.

Tamiflu is the only drug shown to be somewhat effective against H5N1, but there have been several deaths of patients in Asia whose bird flu resisted the drug.

Experts say new flu drugs are urgently needed as at present doctors are limited to one drug, and if the effectiveness of this one drug is lost by so many resistant strains there is no backup antiviral medication against influenza.

The cavity in the N1 enzyme closes to lock on to target proteins in a cell so the virus can get a foothold and infect it, but a new drug could be designed so that its atoms bind more snugly into this active site than Tamiflu and Relenza do and prevent the cavity from shutting.

Such a drug, say the researchers, might avoid the resistance that some influenza viruses have already acquired to Tamiflu.