Identification of a Novel Sulfonamide Non-Nucleoside Reverse Transcriptase Inhibitor by a Phenotypic HIV-1 Full Replication Assay. - Archive ouverte HAL Access content directly
Journal Articles PLoS ONE Year : 2013

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

(1, 2) , (1) , (1) , (1) , (1) , , (1) , , , (1) , (1) , (1) , (2) , , (1)
1
2

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.
Fichier principal
Vignette du fichier
KIMetal2013.pdf (3.92 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

pasteur-00850251 , version 1 (06-08-2013)

Identifiers

Cite

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⟩

Collections

RIIP RIIP_COREE
134 View
226 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More