Journal of Antivirals & Antiretrovirals
Open Access

Aprotinin, a protease inhibitor, as a drug against influenza

International Conference and Exhibition on VIROLOGY

5-7 September 2011 Baltimore, USA

Oleg P. Zhirnov

Scientific Tracks Abstracts: JAA

Abstract :

Research eff orts are focusing on development of new antiviral chemotherapeutic approaches that target either infl uenza virus replication itself or host factor(s) that are critical to infl uenza replication. Host mediated infl uenza hemagglutinin (HA) cleavage critical for activation of virus infectivity is such a chemotherapeutic target. Infl uenza pathogenesis develops through a ?vicious cycle?: host proteases activate progeny virus which amplifi es replication and stimulates protease activities in infected host. Aprotinin, a 58 amino acid polypeptide from bovine lung, is one of a family of the host-targeted antivirals that inhibits serine proteases involved in infl uenza virus activation. Th is drug was shown to suppress virus HA cleavage and multicycle reproduction of human and avian infl uenza viruses with a single arginine in the HA cleavage site. Site-directed structural modifi cations of aprotinin are possible to increase its intracellular targeting against cleavage of highly virulent H5 and H7 hemagglutinins possessing multi-arginine/lysine cleavage site. Additionally, serine protease inhibitors, including aprotinin, are known to target a number of host mediators of infl ammation and down regulates their levels in virus-infected hosts. Aprotinin is a generic drug approved for intravenous use to treat pancreatitis and limit postoperative bleeding. As an antiinfl uenzal compound, aprotinin can be delivered by two routes: (i) a middle-particle aerosol has been used for local respiratory application in mild-to-moderate infl uenza and (ii) an intravenous administration is proposed for severe infl uenza to provide both an antiviral eff ect and a decrease in systemic infl ammation.