title: High-throughput screening method of inhibitors that block the interaction between 2 helical regions of HIV-1 gp41.
abstract: The HIV-1 envelope glycoprotein transmembrane subunit, gp41, mediates the fusion of viral and target cell membranes. The 2 helical regions in the ectodomain of gp41, the N-helix and the C-helix, form a helical bundle complex that has been suggested as a fusion-active conformation. Previously, an enzyme-linked immunosorbent assay (ELISA) method had been established to measure the interaction of 2 helical regions of gp41. In this study, the ELISA method was modified to apply high-throughput screening (HTS) of an organic compound library. A few compounds had been identified to prevent the interaction between 2 helical regions of gp41, and they were further shown to inhibit the gp41-mediated viral infection. In addition, they specifically quenched the fluorescence of tryptophan in the N-helix region, indicating that these compounds bound to the N-helix rather than the C-helix of gp41. These results suggested that this assay method targeting gp41 could be used for HTS of HIV fusion inhibitors.
authors.affiliation: Division of Life Sciences, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Bong-Suk
authors.initials: BS
authors.lastname: Jin
authors.forename: Won-Kyu
authors.initials: WK
authors.lastname: Lee
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
authors.forename: Myung Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Yeon Gyu
authors.initials: YG
authors.lastname: Yu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D014364:Tryptophan