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

Tae-Hee Kim (1, 2) , Yoonae Ko (1) , Thierry Christophe (1) , Jonathan Cechetto (1) , Junwon Kim (1) , Kyoung-Ae Kim , Annette S Boese (1) , Jean-Michel Garcia , Denis Fenistein , Moon Kyeong Ju (1) , Junghwan Kim (1) , Sung-Jun Han (1) , Ho Jeong Kwon (2) , Vincent Brondani , Peter Sommer (1)

1 Institut Pasteur Korea - Institut Pasteur de Corée
2 Department of Biotechnology, Translational Research Center for Protein Function Control

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.

Domaines: Virologie

Tae-Hee Kim, Yoonae Ko, Thierry Christophe, Jonathan Cechetto, Junwon Kim, et al.. Identification of a Novel Sulfonamide Non-Nucleoside Reverse Transcriptase Inhibitor by a Phenotypic HIV-1 Full Replication Assay.. PLoS ONE, 2013, 8 (7), pp.e68767. ⟨10.1371/journal.pone.0068767⟩. ⟨pasteur-00850251⟩