Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative.

Abstract:

A novel 6-substituted acyclouridine derivative, 1-[(2-hydroxy-ethoxy) methyl]-6-phenylthiothymine (HEPT), has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. HEPT inhibits HIV-1 replication in various T4 cell cultures as well as peripheral blood lymphocytes and macrophages. The 50% antiviral effective concentration for HIV-1 (HTLV-IIIB) in MT-4 cells is 7.0 microM, while the 50% cytotoxic concentration for mock-infected MT-4 cells is 740 microM. Although HEPT is inhibitory to various strains of HIV-1, it has no effect on the replication of other retroviruses including HIV type 2. In contrast with the dideoxynucleoside (i.e. azidothymidine) 5'-triphosphates, the triphosphate of HEPT does not interact with HIV-1 reverse transcriptase. The mechanism of action of HEPT remains subject of further study.

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