title: Discovery and optimization of novel small-molecule HIV-1 entry  inhibitors using field-based virtual screening and bioisosteric  replacement.
abstract: With the emergence of drug-resistant strains and the cumulative toxicities associated with current therapies, demand remains for new inhibitors of HIV-1 replication. The inhibition of HIV-1 entry is an attractive, yet underexploited therapeutic approach with implications for salvage and preexposure prophylactic regimens, as well as topical microbicides. Using the combination of a field-derived bioactive conformation template to perform virtual screening and iterative bioisosteric replacements, coupled with in silico predictions of absorption, distribution, metabolism, and excretion, we have identified new leads for HIV-1 entry inhibitors.
authors.forename: Marina
authors.initials: M
authors.lastname: Tuyishime
authors.forename: Matt
authors.initials: M
authors.lastname: Danish
authors.forename: Amy
authors.initials: A
authors.lastname: Princiotto
authors.forename: Marie K
authors.initials: MK
authors.lastname: Mankowski
authors.forename: Rae
authors.initials: R
authors.lastname: Lawrence
authors.forename: Henry-Georges
authors.initials: HG
authors.lastname: Lombart
authors.forename: Kirill
authors.initials: K
authors.lastname: Esikov
authors.forename: Joel
authors.initials: J
authors.lastname: Berniac
authors.forename: Kuang
authors.initials: K
authors.lastname: Liang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ji
authors.forename: Roger G
authors.initials: RG
authors.lastname: Ptak
authors.forename: Navid
authors.initials: N
authors.lastname: Madani
authors.forename: Simon
authors.initials: S
authors.lastname: Cocklin
mesh_terms: D055808:Drug Discovery; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008968:Molecular Conformation
chemical_list: D023581:HIV Fusion Inhibitors