# 1990
The idea that a cocktail of antivirals might be more effective for pandemic influenza, or that one of our antivirals might be rendered ineffective by a viral mutation, is hardly `news'. It has been discussed here, and in far more prestigious venues for years.
Already, in some hot zone countries, Amantadine is sometimes administered along with Oseltamivir (Tamiflu TM).
But Amantadine, which has the advantage of being cheap and easy to manufacture, suddenly lost its effectiveness against seasonal influenza beginning about 4 years ago. It is widely believed that overuse, and reports that Amantadine may have been added as a prophylactic in Chinese chicken feed, hastened its demise as a front line drug.
Some clades of the H5N1 virus are still sensitive to Amantadine, while others are not. Clearly, while Amantadine may have some limited role in a pandemic, it would be foolish to rely heavily on it.
Over the past year suddenly we've seen a major rise in resistance to Oseltamivir among the seasonal flu viruses, and occasionally in cases of human H5N1 infection. With 60% of all H5N1 cases succumbing, even with Tamiflu, there are concerns that may not be working as well as perhaps, another antiviral might.
The problem is, there are few choices available today as an alternative.
Permavir, now under study, and available only as an injectable, has been dissappointing in early trials.
And that pretty much leaves GlaxoSmithKline's Relenza, a powder that must be inhaled deep into the lungs which is considered more difficult to deliver than a pill.
Here is the BBC's report on the latest research.
Single anti-flu drug 'not enough'
Updated at 00:20 GMT, Thursday, 15 May 2008 01:20 UK
No single drug alone will be enough to treat all the victims of a global flu pandemic, research has shown.
Tests on the H5N1 strain of bird flu, which has spread in south east Asia, have shown it is developing resistance to the leading anti-viral drug Tamiflu.
The Nature study, by the Medical Research Council, stresses the need to stockpile more than one type of drug.
The UK government - which has stockpiled millions of doses of Tamiflu - is reviewing its position.
It has already received advice that a one-drug strategy may be flawed.
Number of cases
In order not to be outflanked by the virus, it will be necessary to have stocks of both existing drugs
Dr Steve Gamblin
<snip>
Tamiflu and another drug, Relenza, work by inhibiting a key part of flu called neuraminidase (N1) which is responsible for the release of the virus from infected human cells and allows the disease to spread.
The team at the National Institute for Medical Research found that when they used a method called X-ray crystallography they were able to characterise a mutation in the structure of N1 that has been observed in human cases of H5N1.
The scientists discovered that when this mutation occurred the virus became resistant to Tamiflu, while still remaining susceptible to Relenza.
<snip>
Professor John Oxford, Queen Mary College
Professor John Oxford, an expert in Virology at Queen Mary College School of Medicine London, said: "I don't think it should worry people because these drug resistant mutant strains of H5N1 don't spread very much and are not in the majority, they are still very much in the minority. The majority are still susceptible to anti-viral drugs."
A spokesperson for the Department of Health said: "We are considering how much of our stockpile should consist of a back-up anti-viral."
