The World Health Organization (WHO) is reporting 31 strains of the H1N1 virus which have mutated and are now resistant to the anti-viral drug Tamiflu (oseltamivir). Since the outbreak of the current H1N1 pandemic Tamiflu has been at the front line of defense. Tamiflu is an antiviral drug which is capable of preventing someone from catching H1N1, (if taken within the first 48 hours after an individual has been exposed), reducing the duration and severity of the illness, and decreasing the risk of passing H1N1 on to others. Many health care workers have been taking Tamiflu to prevent catching H1N1 themselves.
Fortunately all 31 strains show a similar mutation and are still susceptible to another antiviral drug called Relenza (zanamivir). As of October 4, 2009 the WHO has reported 4,500 deaths worldwide. They also state that many countries have stopped documenting individual cases because many are mild and require no medical intervention. To date they are estimating 350,000 cases of H1N1 worldwide but state that this number is significantly lower than the actual number of cases occurred.
Stay Up To Date: Subscribe to my free newsletter
and follow me on Twitter or Facebook.
Have Questions? Find out answers to your specific questions on my forum and get support from others.
Tamiflu resistance was always a concern while Relenza was recognised as being superior. Relenza was the first NI antiviral and it was deliberately designed to overcome resistance, Tamiflu was deliberately designed to work in pill form, resistance was a secondary consideration which has only recently become significant with the emergence of deadly bird flu and to a lesser degree swine flu.
Articles have reported on the significant differences from the beginning. An eloquent analysis was published in 2005(one of many in academic circles),
“One strength of the neuraminidase inhibitors oseltamivir and zanamivir (Relenza) over the older adamantanes is that they are less prone to selecting for resistant influenza viruses. Indeed, no virus resistant to zanamivir, which is currently available only in an inhaled form, has yet been isolated from immunocompetent patients after treatment. The recent emergence of oseltamivir-resistant variants is therefore a matter of immediate concern.
Why is resistance developing to oseltamivir? Several years ago,structural analysis predicted that aspects of the chemical structure of oseltamivir (not present in zanamivir) could facilitate the development of resistance mutations that would permit neuraminidase to function, allowing drug-resistant virus to survive and propagate. This prediction is now being validated by clinical data.
The mechanism of the development of resistance is illustrated in the diagram. The influenza neuraminidase releases newly formed viruses from infected cells, allowing them to spread from cell to cell. The inhibitor molecules mimic the natural substrate of the influenza neuraminidase (the sialic acid receptors) and bind to the active site, preventing neuraminidase from cleaving host-cell receptors and releasing new virus. All the resistant variants thus far have contained specific mutations in the neuraminidase molecule; but since neuraminidase serves an essential purpose, mutations that allow the virus to survive must not inactivate the enzyme.
To accommodate the bulky side chain of oseltamivir in the active site, the neuraminidase molecule must undergo rearrangement to create a pocket (Panel A). Zanamivir, by contrast, binds to the active site without any rearrangement of the molecule. Several mutations that limit the necessary molecular rearrangement may diminish the binding of oseltamivir (Panel B). Molecular-level analysis (Panel C) shows that the amino acid termed E276 must rotate and bond with R224 to form a pocket for the side chain of oseltamivir. The mutations R292K, N294S, and H274Y inhibit this rotation and prevent the pocket from forming, resulting in resistance to oseltamivir. The mutations nonetheless allow the binding of natural sialic acid substrate, so mutated virus can survive and propagate. In contrast, the binding of zanamivir does not require any reorientation of amino acids, so these mutated viruses remain sensitive to that drug. An E119V mutation also interferes only with oseltamivir binding, possibly because a water molecule can fit between oseltamivir and valine at the active site but cannot insinuate itself between zanamivir and valine at residue 119.
These mechanisms have clinical implications. The mutations identified in the resistant viruses have thus far all been in the amino acids mentioned above.
http://content.nejm.org/cgi/content/full/353/25/2633
Antiviral information, particularly in the U.S. has been heavily funded by Roche and parroted by health professionals (including the WHO, FDA and CDC), which has resulted in an unhealthy reliance on Tamiflu.