Identification of a Novel Sulfonamide Non-Nucleoside Reverse Transcriptase Inhibitor by a Phenotypic HIV-1 Full Replication Assay. e68767

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 sc...

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Bibliographic Details
Published in:PloS one 2013-07, Vol.8 (7)
Main Authors: Kim, Tae-Hee, Ko, Yoonae, Christophe, Thierry, Cechetto, Jonathan, Kim, Junwon, Kim, Kyoung-Ae, Boese, Annette S, Garcia, Jean-Michel, Fenistein, Denis, Ju, Moon Kyeong
Format: Article
Language:English
Subjects:
Human immunodeficiency virus
Human immunodeficiency virus 1
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Summary: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.
ISSN:1932-6203
DOI:10.1371/journal.pone.0068767