Bird Flu Pandemic Would Require Multi-Drug Approach, UK

Scientists have uncovered a change in the H5N1 bird flu virus which makes it resistant to the anti-viral drug Tamiflu. The mutation in the N1 component was found in human cases of the disease and suggests that a single drug approach is likely to be ineffective in case of a bird flu pandemic in humans. The findings by a team at the Medical Research Council's National Institute for Medical Research are published in Nature.


The research looked at the structure of the flu neuraminidase (N1) which is the target for both Tamiflu and Relenza, the two existing flu drugs. Both drugs aim to inhibit the N1 which is responsible for the release of the virus from infected human cells and thus allows the disease to spread.


Using a method called X-ray crystallography the scientists looked at a mutation in the structure of N1 neuraminidase that has been observed in human cases of H5N1 and in seasonal flu. They found that when this mutation occurred, the virus became resistant to Tamiflu, while still remaining susceptible to Relenza.


Viruses have a high rate of mutation often adapting to the treatments devised to tackle them. It had previously been thought that this mutation in N1 made it less virulent, but recent research from the United States has shown that the mutation does not reduce the infectiousness of the virus.


The team led by Dr Steven Gamblin also looked at samples from the seasonal flu H1N1 and found that samples showing this mutation were also resistant to Tamiflu. While the proportion of seasonal flu samples showing this resistance varies widely across Europe and is relatively low in the UK, there is no telling how the seasonal virus will evolve next year.


Dr Steve Gamblin said: "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. We understand this is something the Government is already exploring. 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."


References:


Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants
Collins et. al. is published online at nature


1. Yen et al Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo. J Virol 81, 12418-12426 (2007).

Medical Research Council


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