tamiflu resistance to human h1n1 answers

Concerning tamiflu resistance. I asked the question on 'Effect Measurea" and got a really interesting response on how relenza binds vs tamiflu. Its long winded but fasinating and worth reading.

""Other questions on tamiflu and relenza: these are different drugs and bind to NA in different ways. Tamiflu was designed for group 2 NA, but a conformation change (an internal rotation) when tamiflu binds makes it look more like group 2 and allows it to bind to N1, too. A common mutation (H274Y) prevents the rotation. Relenza, however, can still bind. But Relenza cannot be absorbed orally so it has to be inhaled with a special inhaler. It is not a pill. Children have difficulty getting this into their lungs as do people with breathing difficulty and asthmatics.

Seasonal H1N1 this year carries the H274Y mutation, but the NA in swine flu, so far, does not. It is not at all anomalous because the NA in the swine flu virus is not derived from the NA in H1N1, it is a swine, not a human NA.""



And this answer :

''From what I've read on the subject (and I'll admit that I've barely skimmed the surface of the literature) the reason for the slower evolution of resistance to Relenza is that while both Relenza and Tamiflu bind strongly to the neuraminidase pocket, the the binding of relenza more closely mimics the binding of sialylglycan to the same pocket. What this means is that there is a high probability that if the virus mutates so that it will no longer bind Relenza it will no longer be able to bind sialylglycan either, so it won't be able to infect cells. With Tamiflu the probability of this happening is a bit lower, though of course many mutations will still block sialylglycan binding, and resistance evolved more quickly. Relenza does look like being the better drug.

It's also worth mentioning that even before the problem of resistance developed neuraminidase N1 was found to be somewhatmore sensitive to Relenza, while neuraminidase N2 was a little more sensitive to Tamiflu, again this would argue that Relenza would be the better drug to use in this outbreak, though both are certainly helpful.""