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Newly described 'dragon' protein could be key to bird flu cure
July 16, 2008Scientists and researchers have taken a big step closer to a cure for the most common strain of avian influenza, or "bird flu," the potential pandemic that has claimed more than 200 lives and infected nearly 400 people in 14 countries since it was identified in 2003.
Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory, in conjunction with scientists from China and Singapore, have crystallized and characterized the structure of one of the most important protein complexes of the H5N1 virus, the most common strain of bird flu.
All viruses, including H5N1, contain only a small number of proteins that govern all of the viruses' functions. In H5N1, perhaps the most important of these proteins is RNA polymerase, which contains the instructions that allows the virus to copy itself along with all of its genetic material. The Argonne study focused on H5N1's RNA polymerase protein, which contains three subunits: PA, PB1 and PB2.
After performing X-ray crystallography on the protein crystals at Argonne's Structural Biology Center 19ID beamline at the Advanced Photon Source, the researchers saw a surprising resemblance in the protein structure's image. "When we mapped out the PA subunit, it looked very much like the head of a dragon," said Argonne biophysicist Andrzej Joachimiak. "One domain looked like the dragon's brains, and the other looked like its mouth."
During RNA replication - the phase during which the virus "reproduces" - all three of the subunits of the protein assemble themselves in a particular configuration. In order for this congregation to take place, the researchers determined the end of the PB1 subunit has to insert itself and bind to the "dragon's mouth" part of the PA subunit.
This unexpected relationship between the two subunits could inspire a number of different therapies or vaccines for H5N1 that rely on muzzling the "dragon's" jaws with another molecule or chemical compound that would block the PB1 subunit's access to the PA site, according to Joachimiak. "If we can put a bit in the dragon's mouth, we can slow or even potentially someday stop the spread of avian flu," he said. "Since we are talking about a relatively small protein surface area, finding a way to inhibit RNA replication in H5N1 seems very feasible."
Joachimiak hopes to more precisely identify the types of compounds that could inhibit RNA replication in H5N1 by looking at the atomic-level grooves and pockets within the PA "mouth" region. According to Joachimiak, scientists must gain a more thorough understanding of the geometry of that small region in order to effectively synthesize drugs that could prevent the further spread of bird flu.
DOE/Argonne National Laboratory
After performing X-ray crystallography on the protein crystals at Argonne's Structural Biology Center 19ID beamline at the Advanced Photon Source, the researchers saw a surprising resemblance in the protein structure's image. "When we mapped out the PA subunit, it looked very much like the head of a dragon," said Argonne biophysicist Andrzej Joachimiak. "One domain looked like the dragon's brains, and the other looked like its mouth."
During RNA replication - the phase during which the virus "reproduces" - all three of the subunits of the protein assemble themselves in a particular configuration. In order for this congregation to take place, the researchers determined the end of the PB1 subunit has to insert itself and bind to the "dragon's mouth" part of the PA subunit.
This unexpected relationship between the two subunits could inspire a number of different therapies or vaccines for H5N1 that rely on muzzling the "dragon's" jaws with another molecule or chemical compound that would block the PB1 subunit's access to the PA site, according to Joachimiak. "If we can put a bit in the dragon's mouth, we can slow or even potentially someday stop the spread of avian flu," he said. "Since we are talking about a relatively small protein surface area, finding a way to inhibit RNA replication in H5N1 seems very feasible."
Joachimiak hopes to more precisely identify the types of compounds that could inhibit RNA replication in H5N1 by looking at the atomic-level grooves and pockets within the PA "mouth" region. According to Joachimiak, scientists must gain a more thorough understanding of the geometry of that small region in order to effectively synthesize drugs that could prevent the further spread of bird flu.
DOE/Argonne National Laboratory
Bird Flu Current Events and Bird Flu News RSSProtein 'tubules' free avian flu virus from immune recognition
A protein found in the virulent avian influenza virus strain called H5N1 forms tiny tubules in which it "hides" the pieces of double-stranded RNA formed during viral infection, which otherwise would prompt an antiviral immune response from infected cells, said Baylor College of Medicine researchers in an online report in the journal Nature.
'Deadly dozen' reports diseases worsened by climate change
Health experts from the Wildlife Conservation Society today released a report that lists 12 pathogens that could spread into new regions as a result of climate change, with potential impacts to both human and wildlife health and global economies.
Scientists working to protect NI from Bird Flu
Queen's scientists are involved in two international projects aimed to protect Northern Ireland's agri-food industry from Bird Flu and African Swine Fever, a disease which kills pigs.
Discovery opens door for drugs to fight bird flu, other influenza epidemics
Researchers at Rutgers University and The University of Texas at Austin have reported a discovery that could help scientists develop drugs to fight the much-feared bird flu and other virulent strains of influenza.
1918 flu antibodies resurrected from elderly survivors
Ninety years after the sweeping destruction of the 1918 flu pandemic, researchers at Monroe Carell Jr. Children's Hospital at Vanderbilt have recovered antibodies to the virus - from elderly survivors of the original outbreak.
Political borders, health-care issues complicate pandemic planning
Panic, staffing issues and geographic boundaries are some of the challenges that public health experts need to address as they plan for a possible influenza pandemic, according to a new report from Purdue University.
Battling bird flu by the numbers
A pair of Los Alamos National Laboratory researchers have developed a mathematical tool that could help health experts and crisis managers determine in real time whether an emerging infectious disease such as avian influenza H5N1 is poised to spread globally.
Getting wise to the influenza virus' tricks
Influenza is currently a grave concern for governments and health organisations around the world. The worry is the potential for highly virulent bird flu strains, such as H5N1, to develop the ability to infect humans easily. New drugs and vaccines to halt the spread of the virus are badly needed.
New strategies against bird flu
The Spanish flu outbreak of 1918 killed between 30 and 50 million people. In the infected patients, the ultimate cause of death was acute respiratory distress syndrome (ARDS).
New vaccine may give long-term defense against deadly bird flu and its variant forms
A new vaccine under development may provide protection against highly pathogenic bird flu and its evolving forms, according to researchers at Purdue University and the Centers for Disease Control and Prevention who discovered the new preventative drug and have tested it in mice.
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