Aprotinin, a protease inhibitor, suppresses proteolytic activation of pandemic H1N1v influenza virus.

摘要

BACKGROUND: The recent emergence of pandemic influenza virus H1N1v stresses the need for the development of new anti-influenza drugs. METHODS: Host proteases responsible for viral haemagglutinin (HA) cleavage are attractive targets for such drugs. Aprotinin, a natural 58-amino-acid polypeptide from bovine lungs, was chosen for this purpose because it is a drug already approved for human use as an antiprotease compound to treat pancreatitis and bleeding, and because it inhibits a wide spectrum of serine proteases, some of which are involved in influenza virus activation. RESULTS: First, we show that HA of pandemic H1N1v was intensively cleaved and activated in different host systems (human tracheo-bronchial epithelium, human intestinal Caco-2 cells and chicken embryonated eggs). Second, aprotinin inhibited HA cleavage and replication of pandemic influenza virus H1N1v in all host systems, including human tracheo-bronchial epithelium. Third, aprotinin did not induce any apparent toxic side effects in these hosts. CONCLUSIONS: Aprotinin can be considered a promising drug against the novel H1N1v pandemic influenza virus.