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

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

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5 Citations (Scopus)

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.

Original languageEnglish
Article numbere68767
JournalPloS one
Volume8
Issue number7
DOIs
Publication statusPublished - 2013 Jul 18

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kim, T. H., Ko, Y., Christophe, T., Cechetto, J., Kim, J., Kim, K. A., Boese, A. S., Garcia, J. M., Fenistein, D., Ju, M. K., Kim, J., Han, S. J., Kwon, H. J., Brondani, V., & Sommer, P. (2013). Identification of a Novel Sulfonamide Non-Nucleoside Reverse Transcriptase Inhibitor by a Phenotypic HIV-1 Full Replication Assay. PloS one, 8(7), [e68767]. https://doi.org/10.1371/journal.pone.0068767