Fighting ‘flu

Never mind Ebola, its influenza we should be worried about. Don’t get me wrong, Ebola is a serious problem and a tragic disease but with two young children in kindergarten there is much greater chance that the ‘flu and not Ebola will come knocking at our door very soon. Even though the ‘flu does not pose a great health risk to me or my family, I really don’t fancy a week of lying in bed feeling sorry for myself with all the aches and fever that the seasonal ‘flu brings with it. For those less fortunate than me, a bout of the ‘flu can mean some serious health consequences and let’s not even get started on those sudden nasty outbreaks caused when animal strains are transmitted to humans like the recent episodes of pig or bird ‘flu. Since the ‘flu means little more than a few days in bed for the most of us, it is easy to forget that seasonal epidemics result in some 3-5 million cases of severe illness and ca. 250000 – 500000 deaths, across the globe every year. For all our scientific prowess (we did just land a probe on a comet!), there’s actually not a lot we can do about the ‘flu. Seasonal vaccines offer protection against the strains thought to be most prevalent during any one season, and we do have some antiviral drugs to our disposal which can alleviate symptoms and help prevent some serious health problems, but otherwise it’s just rest, bed and Paracetamol.

digitally-colorized transmission electron micrograph (TEM) depicts a small grouping of H1N1 influenza virus particles (CDC)

A digitally-colorized transmission electron micrograph (TEM) depicting a small grouping of H1N1 influenza virus particles (Credit: CDC)

That doesn’t of course mean to say that no one is trying to find a way to stop it in its tracks. After some 20 years of research, a team of researchers at EMBL in Grenoble have today finally published the first complete structure of the influenza polymerase – the enzyme responsible for replicating the viral genomic material and preparing it so that the host cell’s protein production machinery is tricked into making viral proteins. The polymerase is vital for the survival and virulence of the virus and being able to shut this down would mean being able to defeat ‘flu. The team have published structures of bits of the enzyme before, but now with the complete picture, they can see how it all fits and works together and have a greater number of options on how to disarm it. Already they have started trying to find molecules that might be potential anti-viral drugs. The research published today shows the structures from two different Influenza species – one of the polymerase from influenza B, and one from a strain of influenza A recently identified in bats that is genetically very similar to the influenza A in humans. The fast evolving influenza A is the species which causes seasonal epidemics and occasional pandemics. Due to its slower rate of evolution influenza B does not pose such a global health threat. But although today’s research does not show the structure of all important human influenza A species, it shows that all functional parts of the polymerase are very similar in both strains studied and so knowledge gained here can be applied to other influenza variants. In fact the scientists believe the knowledge can be applied to fight other diseases caused by related viruses including Ebola. So let’s hope further breakthroughs are just around the corner and don’t remain out of our reach for another 20 years.

Source Articles
Pflug, Guilligay, Reich & Cusack. Structure of influenza A polymerase bound to the viral RNA promoter. Nature, 19 November 2014.

Reich, Guilligay, Pflug et al. Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature, 19 November 2014.

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