Identification of a novel sulfonamide non-nucleoside reverse transcriptase inhibitor by a phenotypic HIV-1 full replication assay
| Autor: | Jean-Michel Garcia, Vincent Brondani, Ho Jeong Kwon, Yoonae Ko, Moon Kyeong Ju, Sung-Jun Han, Junwon Kim, Peter Sommer, Junghwan Kim, Jonathan Cechetto, Thierry Christophe, Annette S Boese, Kyoung Ae Kim, Denis Philippe Cedric Fenistein, Tae-Hee Kim |
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| Přispěvatelé: | Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP), Department of Biotechnology, Translational Research Center for Protein Function Control, Yonsei University-College of Life Science and Biotechnology, This work was supported by the National Research Foundation of Korea (NRF) grant (No.2010-01103) funded by the Korea government (MEST). HJK was supported by the National Research Foundation of Korea (2010-0017984). |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Viral Diseases
Drug Evaluation Preclinical lcsh:Medicine Virus Replication 01 natural sciences Biochemistry Nucleoside Reverse Transcriptase Inhibitor Drug Discovery lcsh:Science 0303 health sciences Sulfonamides Multidisciplinary Drug discovery Organic Compounds RNA-Directed DNA Polymerase Antivirals 3. Good health Chemistry Infectious Diseases [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Medicine Protein Binding Research Article Biotechnology Organic Sulfur Compounds Drugs and Devices Drug Research and Development Cell Survival High-throughput screening Phenotypic screening Enzyme-Linked Immunosorbent Assay Biology Antiviral Agents Models Biological Microbiology Cell Line Small Molecule Libraries 03 medical and health sciences Virology High-Throughput Screening Assays Humans 030304 developmental biology Organic Chemistry lcsh:R HIV Reverse transcriptase 0104 chemical sciences Multiple drug resistance 010404 medicinal & biomolecular chemistry HIV-1 Classical pharmacology lcsh:Q Medicinal Chemistry |
| Zdroj: | PLoS ONE, Vol 8, Iss 7, p e68767 (2013) PLoS ONE PLOS ONE(8): 7 PLoS ONE, Public Library of Science, 2013, 8 (7), pp.e68767. ⟨10.1371/journal.pone.0068767⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0068767⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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