Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Quinazolines chemical synthesis chemistry pharmacology MeSH
- HIV-1 drug effects metabolism MeSH
- Capsid drug effects metabolism MeSH
- Small Molecule Libraries MeSH
- Anti-HIV Agents metabolism pharmacology MeSH
- Humans MeSH
- Models, Molecular MeSH
- Recombinant Proteins biosynthesis MeSH
- Virus Replication drug effects MeSH
- Reproducibility of Results MeSH
- High-Throughput Screening Assays MeSH
- Thermodynamics MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Quinazolines MeSH
- Small Molecule Libraries MeSH
- Anti-HIV Agents MeSH
- Recombinant Proteins MeSH
Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inhibitor to the C-terminal domain of HIV-1 CA (capsid). Screening of >70000 compounds from different libraries identified 2-arylquinazolines as low micromolecular inhibitors of HIV-1 capsid assembly. We prepared focused libraries of modified 2-arylquinazolines and tested their capacity to bind HIV-1 CA to compete with the known peptide inhibitor and to prevent the replication of HIV-1 in tissue culture. Some of the compounds showed potent binding to the C-terminal domain of CA and were found to block viral replication at low micromolar concentrations.
Chemical Biology Core Facility European Molecular Biology Laboratory 691 17 Heidelberg Germany
Department of Biochemistry Faculty of Science Charles University 128 43 Prague 2 Czech Republic
Department of Organic Chemistry Faculty of Science Charles University 128 43 Prague 2 Czech Republic
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