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Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Machara A,Lux V,Kožíšek M,Grantz Šašková K,Štěpánek O,Kotora M,Parkan K,Pávová M,Glass B,Sehr P,Lewis J,Müller B,Kräusslich HG,Konvalinka J

doi

10.1021/acs.jmedchem.5b01089

subject

Has Abstract

pub_date

2016-01-28 00:00:00

pages

545-58

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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