Influenza Virus Sialidase A Target for Drug Discovery

1 Influenza Virus Sialidase A Target for Drug Discovery 

Department of Medicinal Chemistry, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria, 3052, Australia 

Influenza has probably been in existence for much of the history of man. Evidence of the potentially lethal nature of the disease dates from as early as 430 BC, in the fateful plague of Athens. The 1918-1919 influenza pandemic (Spanish flu) swept across the world in three waves and was responsible, directly or indirectly, for over 20 million deaths [1], Since then at least ten lesser pandemics, and numerous milder more localised epidemics, of influenza have been recorded. As recently as 1989 an outbreak of influenza was reported to have been responsible for about 26,000 deaths in England and 

Wales [2], The term influenza was introduced in Italy in the 15th century to describe an epidemic attributed to the influence of the stars. 

For centuries there was wild speculation about the cause of influenza but the 1918-1919 pandemic placed influenza on the world stage and prompted a substantial research effort to find a preventative agent and/or cure for this fatal disease. It was not until 1933 [3], however, that a virus was identified as the causative agent, which marked the start of a better understanding of the disease. 

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INFLUENZA VIRUS SIALIDASE A TARGET FOR DRUG DISCOVERY... 

The discovery of the potent in vitro sialidase inhibitory activity and in vivo efficacy of zanamivir 12, and the increasing availability of 3D structural data for influenza virus sialidases in the 1990s, particularly with Neu5Ac and various inhibitors bound into the active site, provided a platform for further drug discovery efforts targeting... 

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