title: Footprint-based identification of viral entry inhibitors targeting HIVgp41.
abstract: A targeted virtual screen to the N-helix hydrophobic pocket on HIVgp41 was performed using DOCK followed by re-ranking with a new footprint-based scoring function which employed native gp41 C-helix residues as a reference. Of ca. 500,000 small molecules screened, 115 were purchased, and 7 hits were identified with favorable binding (K(i)), cell-cell fusion (IC(50)), and cytotoxicity (CC(50)) profiles. Three of the seven active compounds would not have been discovered without the use of the footprints, demonstrating the utility of the method for structure-based design when a known reference compound or substrate is available.
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Holden
authors.forename: Harmeet
authors.initials: H
authors.lastname: Kaur
authors.forename: Rashi
authors.initials: R
authors.lastname: Goyal
authors.forename: Miriam
authors.initials: M
authors.lastname: Gochin
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rizzo
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors