Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3'-azido-3'-deoxythymidine.
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.
Johnson
V A
VA
Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Walker
B D
BD
Barlow
M A
MA
Paradis
T J
TJ
Chou
T C
TC
Hirsch
M S
MS
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
D000470:Alkaloids; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D015215:Zidovudine; C037806:castanospermine; D054836:Indolizidines