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--translationalhypusine formation in the intracellular protein eIF-5A,to suppress infections by virases that parasitize eIF-5A to promotetheir own replication. Inhibition of the post-translational formationof hypusine in infected host cells with hypusine inhibitors selectivelysuppresses the production of viral proteins and of infectious viralparticles, and causes, particularly after hypusine inhibitor withdrawal,apoptosis in such virally-infected cells. This agent can be a compoundof Formulae (I) or (II) and derivatives thereof as follows: R1, R2, R3,and R4 each individually represents a hydrogen, an alkyl, alkenyl, oralkoxy group containing 1 to about 8 carbon atoms, an aryl, aralkyl,or cycloalkyl group containing about 5 to 12 carbon atoms, or acarboalkoxy or carbamyl group containing up to 8 carbon atoms, ora peptide or peptidomimetic moiety containing 10 to about 30 carbonatoms.