title: Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3'-azido-3'-deoxythymidine.
abstract: Castanospermine and 3'-azido-3'-deoxythymidine (zidovudine) were evaluated in combination against human immunodeficiency virus (HIV) replication in vitro. Castanospermine and 3'-azido-3'-deoxythymidine inhibited HIV type 1 synergistically in acutely infected H9 cells. In addition, they synergistically inhibited both HIV type 1 and HIV type 2 in peripheral blood mononuclear cells. There were no additional toxic effects of these agents in combination. Drug interactions were evaluated by the median-effect principle and the isobologram technique. Combinations of a glycosylation inhibitor, such as castanospermine, with 3'-azido-3'-deoxythymidine deserve consideration for HIV-related chemotherapeutic intervention.
authors.affiliation: Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
authors.forename: V A
authors.initials: VA
authors.lastname: Johnson
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.forename: M A
authors.initials: MA
authors.lastname: Barlow
authors.forename: T J
authors.initials: TJ
authors.lastname: Paradis
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D065089:Glycoside Hydrolase Inhibitors; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D007212:Indolizines; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*; D054836:Indolizidines
chemical_list: D000470:Alkaloids; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D015215:Zidovudine; C037806:castanospermine; D054836:Indolizidines