title: [Screening of HIV-1 replication inhibitors by using pseudotyped virus system].
abstract: This study is to establish a cell-based pharmacological model targeting HIV-1 replication for compounds screening and to screen compounds randomly selected from compounds library by using this pseudotyped viral system. The cell-based HIV-1 replication pharmacological model was set up by HIV-1 core packed with vesicular stomatitis virus glycoprotein. The level of HIV-1 replication was presented by reporter genes expression (luciferase activity or percentage of GFP positive cells). When a compound has inhibitory effect on VSVG/HIV model, VSVG/MLV model would be used to test for specificity. Vesicular stomatitis virus glycoprotein can efficiently mediate HIV core into a wide range of host cells. Expression level of reporter genes showed dose-dependent manner with virion dilution. Among 500 compounds, three compounds dose-dependently inhibit HIV-1 replication, but not MLV replication. VSVG/HIV pseudotyped viral system can be used as a pharmacological model for HIV-1 replication inhibitor screening. Compounds 2-methylthio-5-(4-methylbenzo)amido-l,3,4-thiadiazole, N-(3-hydroxyphenyl)-2-(4-isobutylphenyl) propionamide, and N-(4-picolyl)-4-methylbenzenesulfonamide can specifically inhibit HIV-1 replication with IC50 of 1.92, 5.38, and 3.39 micromol L(-1) respectively.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Cao
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D016049:Didanosine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D010285:Pseudocowpox Virus; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine