Snapshot Issue 17 December 2005

Neuraminidase

What do Peking duck and the French aperitif pastis have in common? A scent: that of badian – otherwise known as star anis. And if star anis has been of growing interest recently it is less for its spicy perfume than for its antiviral virtues… Indeed, a molecule known as shikimic acid is found in the Chinese star anis and it is from this that the popular drug Tamiflu is designed. Now that the dread of an outbreak of the Avian flu carried by the H5N1 strain is hovering over us, badian has an aftertaste of Tamiflu.

The Avian flu virus makes use of two surface proteins in the process of infection: hemagglutinin and neuraminidase. Hemagglutinin binds to a healthy cell where it initiates infection and virus entry. Once the virus has multiplied inside the cell, copies are freed. That is…almost freed. The new viruses bind to receptors – sialic acid – on the infected cell’s surface. And for infection to pursue, the virus must disengage itself. It does so by way of its neuraminidase which cleaves sialic acid. Once cleaved, the virus is free to infect new healthy cells.

How can infection be checked? It so happens that a molecule which resembles sialic acid can be designed from shikimic acid, which is where star anis and Tamiflu come in. Indeed, Tamiflu tricks the Avian flu virus by mimicking sialic acid. Neuraminidase gets confused and chases after Tamiflu instead of cleaving the true sialic acid. As a consequence, the viruses are trapped on the infected cell’s surface and the organism’s immune system can deal with them all that more easily.

Like most antiviral drugs, Tamiflu has certain advantages over vaccines. The Avian flu virus changes its appearance constantly by modifying its surface hemagglutinins and neuraminidases, which is bad news for the immune system. Tamiflu is seemingly not all that concerned by such transformations because it goes for a part of the neuraminidase which is crucial for infection and hence not subject to much modification. Despite this, an H5N1 virus isolated from a young Vietnamese girl turned out to have acquired resistance to Tamiflu, which is cause for concern. Moreover, Tamiflu seems to be only effective on a moderate scale which is why parallel strategies – such as the production of additional antiviral drugs and the development of vaccines – should be found before the Avian flu becomes pandemic.

Read also : "Avian flu : The new Yellow Peril ?"

Hemagglutinin [Precursor], Influenza A virus (souche H5N1): O56140
Neuraminidase, Influenza A virus (souche H5N1): Q9W7Y7

L'édition française de cette chronique est disponible dans l'Instantanés du mois de Prolune.

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