METHOD OF INHIBITING VIRAL REPLICATION IN EUKARYOTIC CELLS AND OF INDUCING APOPTOSIS OF VIRALLY-INFECTED CELLS

摘要

The present invention is directed to methods which inhibit post-translational hypusine formation in the intracellular protein eIF-5A, to suppress infections by viruses that parasitize eIF-5A to promote their own replication. Inhibition of the post-translational formation of hypusine in infected host cells with hypusine inhibitors selectively suppresses the production of viral proteins and of infectious viral particles, and causes, particularly after hypusine inhibitor withdrawal, apoptosis in such virally-infected cells. This agent can be a compound of Formulae (I) or (II) and derivatives thereof as follows: R1, R2, R3, and R4 each individually represents a hydrogen, an alkyl, alkenyl, or alkoxy group containing 1 to about 8 carbon atoms, an aryl, aralkyl, or cycloalkyl group containing about 5 to 12 carbon atoms, or a carboalkoxy or carbamyl group containing up to 8 carbon atoms, or a peptide or peptidomimetic moiety containing 10 to about 30 carbon atoms.