A*Star Scientists Lead the Way in Deciphering the H1N1 Virus Structural Code

New 3D structural model of critical viral protein presents timely molecular information on the fast evolving H1N1 virus

1. Dr Sebastian Maurer-Stroh and his team of scientists from A*STAR’s Bioinformatics Institute (BII) have become the first in the world to demonstrate how bioinformatics and computational biology can contribute towards managing the H1N1 influenza A[1] virus. They published their complex analysis, entitled, “Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites”, in Biology Direct, a peer-reviewed journal on 20 May 2009.

2. In this paper, Dr Maurer-Stroh and his group showed the evolutionary analysis of a critical protein produced by the 2009 H1N1 influenza A virus strain – neuraminidase – as well as demonstrated the use of a computational 3-dimensional (3D) structural model of the protein. With the model they developed, Dr Maurer-Stroh and his team were able to map the regions of the protein that have mutated and determine if drugs and vaccines that target specific regions of the protein were effective. The team unveiled interesting discoveries such as the following:

a. the neuraminidase structure of the 2009 H1N1 influenza A virus has undergone extensive surface mutations compared to closely related strains eg, the H5N1 avian flu virus or other H1N1 strains such as the 1918 Spanish flu;
b. the neuraminidase of the 2009 H1N1 influenza A virus strain is more similar to the H5N1 avian flu than to the historic 1918 H1N1 strain (Spanish flu);
c. the current mutations of the virus have rendered previous flu vaccinations directed against neuraminidase less effective; and
d. the commercial drugs, namely Tamiflu® and Relenza®, are still effective in treating the current H1N1 virus.

3. Said Dr Frank Eisenhaber, Director of BII, “BII’s H1N1 virus sequence study marks a significant milestone in the use of computational biology methods in understanding how the mutations of the fast evolving influenza virus affect immunogenic properties or drug response. This information helps to develop a strategy for fighting the H1N1 virus and for organising an effective treatment for patients.”


Findings published in record time

4. Equally significant is the speed at which the paper was published – in a mere two weeks from the time the first patient virus samples were made available. Dr Sebastian Maurer-Stroh, Principal Investigator at BII and first author of the paper, said, “Because we were working as a team, driven by the common goal to understand potential risks from this new virus, our group at BII was able to successfully complete this difficult analysis within such a short time”.


Other technologies against H1N1 virus

5. Besides this powerful 3D model by BII, A*STAR scientists have also developed other technologies to tackle the 2009 H1N1 Influenza A virus. They include:

a. a chip[2] that is able to quickly sequence or decode the genes in the flu virus and distinguish between the H1N1, seasonal, and mutated flu strains;
b. a microkit[3] for the detection and identification of the flu virus strain within 2 hours; and
c. a molecular diagnostic assay[4] to distinguish between the H1N1 and seasonal flu strains.

BII’s interactive 3D model is available at the following link:
http://mendel.bii.a-star.edu.sg/SEQUENCES/H1N1/

The research findings described in the press release can be found in the article:
“Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites”, Biology Direct, 4:18.
Authors: Sebastian Maurer-Stroh1,*, Jianmin Ma1, Raphael Tze Chuen Lee1, Fernanda L Sirota1 and Frank Eisenhaber1,2

1Biomolecular Function Discovery Division, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore
2Department of Biological Sciences, National University of Singapore, Singapore

*Corresponding author: Sebastian Maurer-Stroh; sebastianms@bii.a-star.edu.sg


About the Bioinformatics Institute (BII)
The Bioinformatics Institute (BII) is a member of the Agency for Science and Technology Research (A*STAR) Biomedical Sciences Institutes. Funded by the Biomedical Research Council (BMRC) of A*STAR, BII was set up in July 2001 as part of the national initiative to foster and advance biomedical research and human capital for a vibrant knowledge-based Singapore. With a multi-disciplinary focus and collaborative outlook, BII recognises the need for depth and breadth in all its activities for building a thriving world-class biomedical research, graduate training and development hub in Singapore. In addition, BII is proactively involved in building a national resource centre in bioinformatics to meet the evolving needs of the scientific community in Singapore.
For more information about BII, please visit www.bii.a-star.edu.sg

About the Agency for Science, Technology and Research (A*STAR)
A*STAR is Singapore’s lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore’s manufacturing industry and new growth industries. It oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
For more information about A*STAR, please visit www.a-star.edu.sg

[1] Influenza A virus strains are categorized according to two proteins found on the surface of the virus: haemagglutinin (H) and neuraminidase (N). All influenza A viruses contain haemagglutinin and neuraminidase. The structures of these proteins differ from strain to strain eg, swine flu belongs to the H1N1 type, avian flu to H5N1 and the currently dominant seasonal flu belongs to the H3N2 type.
[2] This chip has been developed by scientists at the Genome Institute of Singapore (GIS).
[3] The microkit has been developed by scientists at the Institute of Bioengineering and Nanotechnology (IBN).
[4] This molecular diagnostic assay has been developed by scientists from the Institute of Molecular and Cell Biology (IMCB).