Tamiflu resistance mechanism revealed
Scientists from the California Institute of Technology have identified the molecular changes that aided the rapid spread of a strain of the H1N1 virus resistant to the antiviral drug, Tamiflu.
Scientists from the California Institute of Technology have identified the molecular changes that aided the rapid spread of a strain of the H1N1 virus resistant to the antiviral drug, Tamiflu.
A mutated strain of H1N1 (known as H274Y) has swapped a single amino acid for another within the active site of the neuraminidase, changing the three dimensional configuration of the molecule so that while it is still able to cleave the virus from the sialic acid, it no longer binds so strongly to the Tamiflu molecule. This particular mutation had been recognised for several years, but the presence of the mutation also interfered with the virus’ ability to replicate so had no clinical significance.
During the flu outbreak of 2007-2008 there was a rapid spread in the resistance of the virus to Tamiflu and a second mutation in the amino acid sequence of the neuraminidase active site was noted that made the H274Y strain of the virus able to replicate and spread like the wild-type counterparts.
David Baltimore, representing the team at Caltech said that the research has shown that “mutations are not necessarily ‘good’ or ‘bad’, but their effect may depend on the context in which they appear.”
