New Compounds Block Replication of AIDS and Leukemia Viruses

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Compounds
cell's protein-producing machinery and use it to produce their own protein
building blocks. Myristic acid must be linked to some of these proteins in
order for them to be incorporated into an intact virus. Thus, viral
replication is dependent on linkage of myristic acid to viral proteins.
Scientists in Gordon's lab have been studying the enzyme
N-myristoyltransferase, which links myristic acid to specific viral and
cellular proteins. The new compounds they have synthesized are structurally
similar to myristic acid, yet have different chemical and physical properties.
The enzyme "recognizes" the novel compounds and transfers them to some
cellular and viral proteins. Treatment of cells with these myristic acid
analogs significantly reduces viral replication. At optimal concentrations,
one myristic acid analog reduced HIV replication in vitro by approximately 90
percent with no significant toxicity. These results are quite similar to
those seen when AZT, the "gold standard" among AIDS drugs, was used in the
same experimental model.
The research team showed that members of this class of fatty acid analogs
also inhibit the replication of another retrovirus -- the Moloney murine
leukemia virus -- which causes leukemia in mice. While one analog worked most
effectively against HIV, a different one was more successful against the
Moloney virus. The analogs are produced by substituting sulfur and oxygen for
native atoms at various locations in the myristic acid molecule.

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