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Avian Flu News for Senior Citizens
Discovery of Bird Flu Virus Structure Could Herald
Better Drugs
Tamiflu only drug
shown effective against H5N1, but there were human deaths in Asia where
bird flu resisted the drug
By David
McAlary
Voice of America, Washington - 16 August 2006
 British
researchers have taken a step that could lead to more potent drugs
against the deadly H5N1 bird flu virus. They have peered inside a key
protein on the surface of the virus, obtaining structural information
that chemists could use to design new drugs to block it.
To follow this story, it is necessary for a short
biology lesson.
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on
FLU 2005-06 |
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The H5N1 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 and Relenza, which are being stockpiled by
some countries in case the H5N1 bird flu becomes a human pandemic.
But the problem is that these drugs were designed
on the basis of the atomic structures for two other forms of
neuraminidase in other strains of flu, the only two seen so far through
x-ray microscopes. So no one knows how well these antivirals would
perform against the N1 protein if H5N1 begins to spread easily among
people. Tamiflu is the only drug shown to be somewhat effective against
H5N1, but there have been several deaths of patients in Asia whose bird
flu resisted the drug.
"The reason this is so alarming is that right now,
we really don't have a lot of options," said Anna Moscona.
Pediatrician Anna Moscona of the Weill-Cornell
Medical College in New York City says new flu drugs are urgently needed.
"So we are really limited to this one drug," she
said. "And if we lose the effectiveness of this drug by so many
resistant strains that we no longer can use this drug effectively, then
we are really in trouble. We have no backup antiviral medication against
influenza."
But 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 as
well as that of two other closely related neurominidases. They report in
the journal Nature that the enzymes have 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.
 The cavity in the N1 enzyme closes to lock on to
target proteins in a cell so the virus can get a foothold and infect it.
But a new drug could be designed so that its atoms bind more snugly into
this active site than Tamiflu and Relenza do and prevent the cavity from
shutting.
"It would probably be bigger," he said. "I mean, it
looks at least from the structure as if it would be possible to add more
substituents [atoms], which would then occupy the new cavity specific
for this N1 group of neurominidases. In the first instance, those are
the sorts of drugs you would try to make."
This kind of drug might avoid the resistance that
some influenza viruses have already acquired to Tamiflu.
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 against influenza.
|
Cumulative Number of
Confirmed Human Cases of Avian Influenza
A/(H5N1) Reported to WHO
14 August 2006
|
Country
|
2003 |
2004 |
2005 |
2006 |
Total |
|
cases |
deaths |
cases |
deaths |
cases |
deaths |
cases |
deaths |
cases |
deaths |
|
Azerbaijan |
0 |
0 |
0 |
0 |
0 |
0 |
8 |
5 |
8 |
5 |
|
Cambodia |
0 |
0 |
0 |
0 |
4 |
4 |
2 |
2 |
6 |
6 |
|
China |
1 |
1 |
0 |
0 |
8 |
5 |
12 |
8 |
21 |
14 |
|
Djibouti |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
|
Egypt |
0 |
0 |
0 |
0 |
0 |
0 |
14 |
6 |
14 |
6 |
|
Indonesia |
0 |
0 |
0 |
0 |
17 |
11 |
40 |
33 |
57 |
44 |
|
Iraq |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
2 |
2 |
2 |
|
Thailand |
0 |
0 |
17 |
12 |
5 |
2 |
2 |
2 |
24 |
16 |
|
Turkey |
0 |
0 |
0 |
0 |
0 |
0 |
12 |
4 |
12 |
4 |
|
Viet Nam |
3 |
3 |
29 |
20 |
61 |
19 |
0 |
0 |
93 |
42 |
|
Total |
4 |
4 |
46 |
32 |
95 |
41 |
93 |
62 |
238 |
139 |
Total number of cases includes number
of deaths.
WHO reports only laboratory-confirmed
cases. |
>> For more information, visit
http://www.usda.gov/birdflu or
http://www.avianflu.gov.
>> FACT SHEET:
Avian Influenza Testing And Diagnostics
>>
USDA Bird Flu Information
>>
PandemicFlu.gov & Avian Flu.gov
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