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 Infectious Diseases Virology University Hospital Heidelberg Im Neuenheimer Feld 324 691 20 Heidelberg Germany

Department of Infectious Diseases Virology University Hospital Heidelberg Im Neuenheimer Feld 324 691 20 Heidelberg Germany Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Gilead Sciences and IOCB Research Center Flemingovo n 2 166 10 Prague 6 Czech Republic

Department of Organic Chemistry Faculty of Science Charles University 128 43 Prague 2 Czech Republic

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Gilead Sciences and IOCB Research Center Flemingovo n 2 166 10 Prague 6 Czech Republic

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Gilead Sciences and IOCB Research Center Flemingovo n 2 166 10 Prague 6 Czech Republic Department of Biochemistry Faculty of Science Charles University 128 43 Prague 2 Czech Republic

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$a Štěpánek, Ondřej $u Department of Organic Chemistry, Faculty of Science, Charles University , 128 43 Prague 2, Czech Republic.

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