H5N1 virus proves resistant to anti-flu drug
The H5N1 strain of avian flu, which has proven lethal to humans, can mutate into strains that are resistant to one of only two flu drugs available on the market, new and partly EU-funded research has revealed. The findings, which are reported in Nature, suggest that the most effective way of dealing with a bird flu pandemic would involve stockpiling a combination of anti-viral drugs. The researchers reached their conclusion after studying the molecular structure of neuraminidase, a surface glycol-protein which is responsible for the spread of viruses in humans. The protein does this by removing sialic acid from the cell-surface receptors so that newly-made viruses are released and are able to spread into uninfected cells. Both Tamiflu and Relenza, the only two flu drugs available on the market, target neuraminidase using inhibitors that resemble the sialic acid substrate of the protein. It is thought that the more inhibitors resemble the naturally-occurring protein, the better they will be at combating the virus. In the latest study, the researchers used X-ray crystallography to get at clearer picture of the binding structure of both Tamiflu and Relenza in several human cases of the H5N1 virus, where a mutation in the neuraminidase protein had occurred. They found that mutated strains remained susceptible to Relenza, while Tamiflu proved significantly less effective for two mutated strains. The researchers also tested samples of the seasonal A (H1N1) flu virus strain between November 2007 and January 2008 in 18 European countries. They found that a total of 59 samples from nine different countries were resistant to Tamiflu. 'What this research shows is that stockpiling any one drug to prepare for a potential H5N1 pandemic is unlikely to provide adequate cover. In order not to be outflanked by the virus, it will be necessary to have stocks of both existing drugs,' explains Dr Steve Gamblin of the UK's National Institute for Medical Research, who led the study. 'There is also a huge imperative to develop further drugs that could help disable this protein on the virus surface. It is likely a future pandemic will need to be tackled using a three- or four-pronged approach, much as we tackle HIV today,' he added. According to the latest figures from the World Health Organization, there have been 382 confirmed cases of people becoming infected by the virus and 241 deaths, mainly in South East Asia. The European Commission has funded many research projects targeting influenza, providing funding of over €90 million since 2001. Such research will continue under FP7, and the Commission recently announced the first projects in this area that will receive funding under FP7. Of 44 influenza-related proposals received by the Commission, 11 have been pre-selected for funding. The projects selected are set to receive some €27 million between them, and address issues such as diagnostics, drug and vaccine development and capacity building. EU support for the research came from the EU-funded project 'Vigilance against Viral Resistance' (VIRGIL).