Identification of a novel sulfonamide non-nucleoside reverse transcriptase inhibitor by a phenotypic HIV-1 full replication assay.
PLoS One
; 8(7): e68767, 2013.
Article
em En
| MEDLINE
| ID: mdl-23874756
ABSTRACT
Classical target-based, high-throughput screening has been useful for the identification of inhibitors for known molecular mechanisms involved in the HIV life cycle. In this study, the development of a cell-based assay that uses a phenotypic drug discovery approach based on automated high-content screening is described. Using this screening approach, the antiviral activity of 26,500 small molecules from a relevant chemical scaffold library was evaluated. Among the selected hits, one sulfonamide compound showed strong anti-HIV activity against wild-type and clinically relevant multidrug resistant HIV strains. The biochemical inhibition, point resistance mutations and the activity of structural analogs allowed us to understand the mode of action and propose a binding model for this compound with HIV-1 reverse transcriptase.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Sulfonamidas
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Replicação Viral
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HIV-1
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Avaliação Pré-Clínica de Medicamentos
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Descoberta de Drogas
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
PLoS One
Ano de publicação:
2013
Tipo de documento:
Article