New structural information may help stop the flu

By Yun Xie | Published: July 29, 2008 - 10:47AM CT

Influenza A virus: H5N1.

The Influenza A virus population contains variants and subtypes that have the potential to spread virulently across the globe, including H5N1. A strain of H5N1 is behind the avian flu, which kills over 50 percent of the humans who are infected with it. H5N1 has the potential of mutating to increase its transmission efficiency among humans, making it a major concern for world health.

It is known that there are three subunits (PB1, PB2 and PA) in an Influenza A protein complex that are essential for its replication. The structures of these subunits, however, were not well understood. Thus, it was impossible to create drugs that inhibit their function. Currently, most drugs either target major antigens at the surface of the virus or specific proteins like a proton channel. Antigens and proteins vary among different types of Influenza A, so it is difficult to find drugs that work on all of them and mutations that slightly alter a protein or antigen can easily make drugs useless. Knowing the structures of the Influenza A subunits would open new avenues for drug design.

The binding site of PA(green) and PB1(orange).

In an early release paper that will appear in Nature, scientists from Japan presented the crystal structures of two large fragments of subunits PA and PB1 bound to one another. The binding of PA to PB1 is vital for viral replication and RNA polymerase activity. From the structure, the authors discovered that this crucial interaction comes from an array of hydrogen bonds and hydrophobic interfaces at the binding site. The binding sites that link PA and PB1 are highly conserved, which means that they are very similar for most variants and subtypes of Influenza A. It also means that mutations are less likely to occur in this site.

Because of these features, drugs that can bind and disrupt the interaction of PA and PB1 are likely to be effective against many viral strains and will be less likely to see the virus evolve a resistance to them. The authors' solved structures will serve as a valuable reference point for future drug design.

Nature, 2008. DOI: doi:10.1038/nature07225

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Flu virus research earns NRC honour

Student wins top science prize

Flu virus research earns NRC honour

Chris Maclean, The Ottawa Citizen

Published: Thursday, May 08, 2008

A 17-year-old Ottawa student has won a national science competition with research into diagnosing and possibly preventing the influenza virus.

Maria Merziotis, a Grade 12 student at Hillcrest High School, took the top prize, worth $5,000, at the 2008 Sanofi-Aventis BioTalent Challenge, announced yesterday at National Research Council headquarters. She also won a $1,000 prize for having the project with the most commercial potential.

"I just wanted to create something that would touch on an issue that affects a lot of people," Ms. Merziotis said after the ceremony.

17-year-old Maria Merziotis won a national science competition yesterday for her study that demonstrated the potential of a new way to diagnose, and perhaps prevent, influenza.

Julie Oliver, The Ottawa Citizen

This is not your typical science fair. Students in the competition are assigned a mentor in their community who provides advice and access to equipment and supplies. The students submit research proposals for evaluation by a scientific committee and the results are judged by fellow students and representatives of government, business and academia.

Ms. Merziotis says she worked on her project three days a week for a year. Michel Gilbert of the National Research Council's Institute of Biological Sciences was her mentor on the project, which was dubbed
"Tricking the Influenza virus."

Ms. Merziotis designed a receptor (a form of salic[[sic sialic see - http://en.wikipedia.org/wiki/Sialic_acid]]- acid) for the flu virus that would bind the virus, preventing it from attaching to human cells. The receptor is also able to determine to which strain of the virus it was attached.

"The influenza threat is very serious and it's very important that research like this, on preventing and monitoring it, continues to happen. That's why we chose this topic," said Mr. Gilbert.

The students in the BioTalent Challenge "represent some of the finest young scientists across Canada," said Roman Szumski, vice-president of life sciences at the National Research Council, which hosted the competition results announcement yesterday.

Ms. Merziotis' research has been sent to Health Canada, which has said her application has "encouraging results." Health Canada plans to continue to test her receptor to see how effective it is at preventing and identifying different strains of the influenza virus.

As for Ms. Merziotis?

"I would like to continue studying science, maybe go into medical school or research," she said.

"Curiosity is what binds all scientists, and I love trying to find answers, so, hopefully, I'll continue doing that."

As for the money, Ms. Merziotis says she plans to save it for university.

Ms. Merziotis and the second-place team, a trio of students from the University of Toronto School, will represent Canada at the international BioGENEius Challenge in San Diego, California, from June 16-18.

© The Ottawa Citizen 2008

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