Influenza is a common viral infection affecting about 10% to 20% of the US population each year. As a result an average of about 20,000 people per year will die and 114,000 per year have to be admitted to the hospital. Anyone can get the flu and serious problems from flu can happen at any age although the elderly, people with chronic medical conditions, and very young children are more likely to get complications from flu.

The clinical approach to influenza relies heavily on prevention and the development of vaccines however protection is limited following the emergence of new viral strains. Treatment is usually symptomatic although the launch of Relenza (Zanamivir), Biota’s neuraminidase inhibitor, in 1999 offers clinicians a tool for reducing the duration of symptoms in individuals infected by the influenza virus. Relenza must however be administered through the use of an inhaler and is expensive leading to its restricted use in some countries. Furthermore, Relenza may cause bronchospasm in patients with severe asthma or COPD. New approaches to the treatment of influenza infection are therefore being sought.

Influenza viruses have two principal surface glycoproteins. Like neuraminidase, hemagglutinin also permits the virus to attach to and infect hosts and both are targets of significant host immunologic responses. The development of inhibitors able to block host proteases that activate hemagglutinin represents a therapeutic strategy. However, until recently the host proteases responsible for this activity have remained unclear. This has now been addressed by researchers at Sankyo who have recently isolated a 32 kDa protein from porcine lungs, which possess hemagglutinin processing activity. In their most recent publication, Sato et al report the purification of another hemagglutinin processing enzyme from porcine lung. The purified 28.5-30 kDa enzyme, named tryptase TC30, cleaves peptide substrates with Arg at the P1 position, and preferentially substrates with the Ser-Ile-Gin-Ser-Arg sequence corresponding to the hemagglutinin cleavage site sequence of the A/PR/8/34 influenza virus. Among various inhibitors tested, trypsin-type serine protease inhibitors, such as aprotinin, antipain, benzamidine and leupeptin, efficiently inhibited the proteolytic activity of the enzyme. The N-terminal 40 amino acid sequence of tryptase TC30 exhibits more than 60% homology to mast cell tryptases from mice MCP-6 and human tryptase-alpha and -beta. These data indicate that tryptase TC30 is a novel hemagglutinin-cleaving enzyme and the development of small molecule inhibitors is eagerly awaited.

Entry date Monday, May 19, 2003

Adapted from Sato et al, Biol Chem 2003 Feb;384(2):219-27 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk