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

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 virus.

The team has published its 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.

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:

• 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;

• 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);

• the current mutations of the virus have rendered previous flu vaccinations directed against neuraminidase less effective; and

• the commercial drugs, namely Tamiflu® and Relenza®, are still effective in treating the current H1N1 virus.

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 organizing an effective treatment for patients.”

Findings published in record time

• 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

• 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 chip that is able to quickly sequence or decode the genes in the flu virus and distinguish between the H1N1, seasonal, and mutated flu strains;

- a microkit for the detection and identification of the flu virus strain within 2 hours; and

- a molecular diagnostic assay to distinguish between the H1N1 and seasonal flu strains.