Avian flu’s Achilles’ heel, Stopping the silent spread

The molecular structure of a key avian influenza protein reveals a quirk that could be used to design more potent drugs against pandemic flu; The use of unvaccinated 'sentinel' birds may not always prevent the silent spread of the H5N1 virus through vaccinated flocks


This press release is copyright Nature. VOL.442 NO.7104 DATED 17 AUGUST 2006

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Immunology: Avian flu’s Achilles’ heel

Avian flu: Stopping the silent spread

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[2] Immunology: Avian flu’s Achilles’ heel (AOP)
DOI: 10.1038/nature05114

***This paper will be published electronically on Nature's website on 16 August at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 17 August, but at a later date.***

The molecular structure of a key avian influenza protein reveals a quirk that could be used to design more potent drugs against pandemic flu, report John Skehel and his colleagues in a paper to be published online this week by Nature.

The H5N1 virus that is spreading around the globe gets its initials from the haemagglutinin (H) and neuraminidase (N) proteins on the coat of the virus, and each protein comes in several different forms. The neuraminidase helps the virus to escape infected cells and attack new ones, and is targeted by the drugs oseltamivir (Tamiflu) and zanamivir (Relenza). But these drugs were designed on the basis of the crystal structures for neuraminidases N2 and N9 — the only structures available until now.

The structure of the N1 enzyme — and closely related N4 and N8 enzymes — exposes a key difference in enzyme configuration when compared with the previous structures: a cavity in one corner of the active site that closes when it locks onto its target proteins. This difference could potentially be exploited to design much-needed drugs that bind more snugly into this active site, and perhaps sidestep the drug resistance that some viruses have already acquired to Tamiflu.

John Skehel (National Institute of Medical Research, London, UK)
Tel: +44 20 8816 2525; E-mail: [email protected]

[3] Avian flu: Stopping the silent spread (p757)

The use of unvaccinated 'sentinel' birds may not always prevent the silent spread of the H5N1 virus through vaccinated flocks, according to a Brief Communication in Nature this week. There are growing concerns that, despite effective protection in individual birds, vaccination may not be sufficient to stop outbreaks across an entire flock, with transmission of the virus going undetected.

Nicholas J. Savill and colleagues used mathematical modelling of data to track the spread of H5N1 through flocks. They report that 90% of birds need to be protected to reduce the probability of an outbreak by 50%, but that this could increase the risk of outbreaks escaping detection. They show that although outbreaks become less likely within the flock itself, there is a higher chance of between-flock transmission.

The practice of placing and monitoring unvaccinated sentinel birds in flocks can mitigate, but not completely eliminate, these negative effects. A highly effective vaccine and vaccine delivery system must be combined with rapid detection and removal of infected flocks, the team concludes.

Nicholas Savill (University of Edinburgh, Edinburgh, UK)
Tel: +44 131 6507573; E-mail: [email protected]


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Published: 16 Aug 2006

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