title: Identification of a small molecule HIV-1 inhibitor that targets the capsid hexamer.
abstract: The HIV-1 CA protein is an attractive therapeutic target for the development of new antivirals. An inter-protomer pocket within the hexamer configuration of the CA, which is a binding site for key host dependency factors, is an especially appealing region for small molecule targeting. Using a field-based pharmacophore derived from an inhibitor known to interact with this region, coupled to biochemical and biological assessment, we have identified a new compound that inhibits HIV-1 infection and that targets the assembled CA hexamer.
authors.affiliation: Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Rooms 10302-10306, 245 North 15th Street, Philadelphia, PA 19102, USA.
authors.forename: Jimmy P
authors.initials: JP
authors.lastname: Xu
authors.affiliation: Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Rooms 10302-10306, 245 North 15th Street, Philadelphia, PA 19102, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Branson
authors.affiliation: Cresset, New Cambridge House, Bassingbourn Road, Litlington, Cambridgeshire SG8 0SS, UK.
authors.forename: Rae
authors.initials: R
authors.lastname: Lawrence
authors.affiliation: Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Rooms 10302-10306, 245 North 15th Street, Philadelphia, PA 19102, USA. Electronic address: scocklin@drexelmed.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Cocklin
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D036022:Capsid Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D020836:Protein Structure, Quaternary; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D036022:Capsid Proteins; D054852:Small Molecule Libraries
keywords: Antiviral; Computer-aided drug design; Field-based virtual screening; HIV-1 capsid protein; Surface plasmon resonance