The UK has stockpiled millions of doses of tamiflu
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
The latest figures for human cases of the H5N1 bird flu virus show 382 people have been infected and 241 killed, mostly in south east Asia.
However the virus cannot easily pass from human to human at present.
So far many of those who have been infected have been poultry workers who have come into intimate contact with infected birds.
Experts warn that if the virus acquires the ability to pass from human to human, then it will pose a potential threat to millions across the globe.
Health chiefs in the UK have warned that if such a modified strain does emerge, tens of thousands of people could die in Britain alone.
In this instance health authorities hope stockpiles of anti-viral drugs will help treat those affected.
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.
They also looked at samples from seasonal influenza, that affected people across Europe earlier this year, and found that samples showing this mutation were also resistant to Tamiflu.
Dr Steve Gamblin, who led the research team said it shows that stockpiling any one drug to prepare for a potential H5N1 pandemic is unlikely to provide adequate cover.
He said: "In order not to be outflanked by the virus, it will be necessary to have stocks of both existing drugs.
"There is a huge imperative to develop further drugs and it is likely a future pandemic will need to be tackled using a three or four-pronged approach, much as we tackle HIV today."
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."