HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.
An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system.
D000956:Antigens, Viral / Q000096:biosynthesis; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D001667:Binding, Competitive; D002459:Cell Fusion / Q000187:drug effects; D002845:Chromatography; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000494:pharmacology; D017245:Foscarnet / Q000494:pharmacology; D005707:Gallic Acid / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D010936:Plant Extracts / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine / Q000494:pharmacology
D000956:Antigens, Viral; D001578:Benzopyrans; D016655:HIV Core Protein p24; D010936:Plant Extracts; D018894:Reverse Transcriptase Inhibitors; C079484:repandusinic acid A; D004610:Ellagic Acid; D017245:Foscarnet; D015215:Zidovudine; D005707:Gallic Acid; D054303:HIV Reverse Transcriptase; D004259:DNA-Directed DNA Polymerase; D005947:Glucose