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AssigneeCornell Research Foundation, Inc.
InventorsHartmut M. Hanauske-Abel, Robert Walter Grady, Axel Hanauske, Linda Andrus, Paul Szabo
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The present invention is directed to methods which employ inhibition of the post-translational hypusine formation in the intracelluar protein eIF-5A, for the purpose of suppressing infections by viruses that parasitize eIF-5A so as to promote their own replication. Intentional inhibition of the post-translational formation of hypusine in infected host cells with compounds generically termed `hypusine inhibitors` not only selectively suppresses the production of viral proteins and of infectious viral particles, but also causes, particularly after hypusine inhibitor withdrawal, apoptosis in such virally-infected cells. Each of these methods, respectively, involves administering, to eukaryotic cells, tissues, or individuals, an agent which blocks the post-translational intracellular formation of hypusine, in an amount sufficient to: suppress biosynthesis of bioactive eIF-5A, suppress translational interaction of eIF-5A with viral elements of nucleic acid and/or protein structure, inhibit biosynthesis of viral proteins of Rev-dependent lentiviruses or of viruses dependent on interaction of eIF-5A with viral elements of nucleic acid and/or protein structure, inhibit replication of Rev-dependent lentiviruses or of viruses dependent on interaction of eIF-5A with viral elements of nucleic acid and/or protein structure, and induce apoptosis of virally-infected cells. This agent can be a compound of Formulae I or II and derivatives thereof as follows: ##STR1## R.sub.1, R.sub.2, R.sub.3, and R.sub.4 each individually represent 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.
A method of inhibiting intracellular synthesis of functional eIF-5A comprising:
A method of inhibiting translationally productive interaction of eIF-5A with viral elements of nucleic acid and/or protein structure comprising:
A method of inhibiting biosynthesis of viral proteins of Rev-dependent lentiviruses or of viruses dependent on interaction of eIF-5A with viral elements of nucleic acid and/or protein structure comprising:
A method of inhibiting replication of Rev-dependent lentiviruses or viruses dependent on interaction of eIF-5A with viral elements of nucleic acid and/or protein structure comprising:
A method of inducing apoptosis in cells infected with Rev-dependent lentiviruses or viruses dependent on interaction of eIF-5A with viral elements of nucleic acid and/or protein structure comprising:
Dependencies are inferred from the claim text.