The war against influenza: discovery and development of sialidase inhibitors

The threat of an influenza pandemic has heightened the need for therapeutic strategies to combat this virus. This article provides a historical perspective on the discovery and development of two drugs that are at the forefront of our defences against influenza — the sialdiase inhibitors zanamivir and oseltamivir — highlighting the value of structure-based drug design in this process. The threat of a major human influenza pandemic, in particular from highly aggressive strains such as avian H5N1, has emphasized the need for therapeutic strategies to combat these pathogens. At present, two inhibitors of sialidase (also known as neuraminidase), a viral enzyme that has a key role in the life cycle of influenza viruses, would be the mainstay of pharmacological strategies in the event of such a pandemic. This article provides a historical perspective on the discovery and development of these drugs — zanamivir and oseltamivir — and highlights the value of structure-based drug design in this process.