According to the study, though the required gene mutations are just five, it is unclear whether this can happen outside the laboratory.
At present, H5N1 affects a person mostly if he has had contact with sick or dead infected poultry. Otherwise it is not infectious in humans and it does not spread through air. .
The H5N1 bird flu is known to have affected 650 people across the globe till now and of these 386 died. It was first identified in Hong Kong 17 years ago.
The virus is so deadly that scientists at one point had stalled research on it because they worried that if landed in wrong hands it could be used as a biological weapon.
"The biggest unknown is whether the viruses are likely to gain the critical mutations naturally," says Richard Webby, a virologist at St Jude Children's Research Hospital in Memphis. "If they can appear readily, then it is very worrisome. If not, then there's still a major hurdle that these viruses have to get over to become human-transmissible."
For the study, the scientists used ferrets as the stand-in for humans as their immune system responds to the disease just like humans'. By using various genetically altered viruses on ferrets and human tissue samples, scientists identified five major gene mutations.
The study was published in journal Cell.