Researchers target possible weakness in AI virus
British researchers have made a discovery that could lead to more
effective drugs against the deadly H5N1 bird flu
They have examined a key protein on the surface of the virus, obtaining
structural information that chemists could use to design new drugs to block it.
The researchers have discovered a that there is a cavity in the N1 enzyme
that closes to lock on to target proteins in a cell so the virus can get a
foothold and infect it. A new drug could be designed so that its atoms bind more
snugly into this active site and prevent the cavity from shutting.
The H5N1 avian
influenza virus spreading around the globe has a surface protein whose job
is to help the virus enter and infect cells. This protein is called
neuraminidase, the N1 in H5N1. This is the enzyme targeted by the drugs Tamiflu
But Tamiflu and Relenza, which are being stockpiled by some countries in case
the H5N1 bird flu becomes a human pandemic, were designed on the basis of the
atomic structures for two other forms of neuraminidase in other strains of flu,
N2 and N9, the only two seen at that stage through x-ray microscopes.
Hope for better drugs now comes from a team led by John Skehel of the British National Institute of
Medical Research. The scientists have used the x-ray technology to determine
N1's shape. They report in the journal Nature that the enzyme has a key
structural difference from the two neurominidases studied earlier.
"It turns out that, unlike the previously determined structures, the
structure of the N1 and the other members of this group have a cavity next to
the active site of the enzyme, which might be able to be used to develop other
drugs than the ones that are currently available," said John Skehel.
This kind of drug might avoid the resistance that some influenza viruses have
already acquired to Tamiflu. It's possible that new drugs might work in tandem
with Tamiflu and Relenza to overcome resistance to those agents. "It would be a
combination therapy like you have in HIV," Skehel explained.
Skehel says new drugs are at least five years away. Still, a Nature magazine
commentary by University of Alabama
microbiologist Ming Luo says the work provides valuable intelligence in the war
Image courtesy of 3dscience.com
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