Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication.
Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting activity of its LTR. We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At these concentrations, each drug inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1. Their target is transcriptional function of the LTR.
Li
C J
CJ
Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Zhang
L J
LJ
Dezube
B J
BJ
Crumpacker
C S
CS
Pardee
A B
AB
D000208:Acute Disease; D000998:Antiviral Agents; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002908:Chronic Disease; D003474:Curcumin / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D066298:In Vitro Techniques; D009285:Naphthoquinones / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis; D019772:Topotecan; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009285:Naphthoquinones; D012367:RNA, Viral; C014638:beta-lapachone; D019772:Topotecan; D003474:Curcumin; D002166:Camptothecin