Neuraminidase – complicated but very important

What am I looking at?

How do we know why blood is red, and how many medicines work to make us feel better?  Well this and thousands of other discoveries have come from understanding the crystal structure of proteins.  Proteins are the building blocks of all life, but are large and squishy (relatively speaking) so it was hard to represent these with plastic like we have for the other giant structure.  Instead, we turned to knitting, and asked UK-based fibre artist Madeleine Shepherd to make us this knitted neuraminidase.

This is a representation of Neuraminidase, a molecule that sits on the surface of the flu virus and is vital in how the virus infects people and animals.  What are also represented here are four molecules of the Relenza drug, the blue bits sitting in the four sections of the molecule.  This is a drug which was specifically designed to stop Neuraminidase doing its job and infecting people with flu!

Our model of Neuraminidase is about 1 metre across, but sitting on the flu virus this would be 100 million times smaller.

Why is this crystal structure important?

Swine flu, bird flu, and ‘man’ flu. They are all caused by the Influenza virus. The flu virus is continually changing. What we do know is that there are two molecules, hemagglutinin and neuraminidase, that sit on the surface of the virus and are critical for infection. Hemagglutinin is responsible for binding to the cells in our body, so that the virus can then inject its viral genome into our cells. Neuraminidase helps to disengage the virus from our cells. The enzyme clips off the chains that anchor the virus to the cell. By blocking the action of neuraminidase, we can stop viral release and spread, and so it has been an important target for drugs targeting the flu.

What’s going on in Australia with this material?

The structure of influenza virus A/Tokyo/3/67 neuraminidase was solved in 1991 by two Australian scientists (Peter Malcolm Colman and Joseph Varghese) (http://www.ncbi.nlm.nih.gov/pubmed/1920428). Since then, many other varieties of flu neuraminidase have been solved, including the swine flu neuraminidase.

In 1989, scientists at the CSIRO (led by Peter Malcolm Colman and Joseph Varghese) in collaboration with the Victorian College of Pharmacy, Monash University, and Glaxo in the UK, developed the first neuraminidase inhibitor, Zanamivir (marketed as Relenza). Its discovery relied heavily on the availability of the structure of influenza neuraminidase.