Screening of HIV-1 replication inhibitors by using pseudotyped virus system.
- Author:
Ying-Li CAO
1
;
Ying GUO
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Anti-HIV Agents;
pharmacology;
DNA Replication;
drug effects;
Didanosine;
pharmacology;
Drug Evaluation, Preclinical;
methods;
Genes, Reporter;
drug effects;
genetics;
HIV-1;
drug effects;
physiology;
Humans;
Lamivudine;
pharmacology;
Pseudocowpox Virus;
Tumor Cells, Cultured;
Virus Replication;
drug effects;
Zidovudine;
pharmacology
- From:
Acta Pharmaceutica Sinica
2008;43(3):253-258
- CountryChina
- Language:Chinese
-
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.
