title: Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS.
abstract: Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development.
authors.affiliation: Laboratory of Antiviral Drug Mechanisms, PRI/DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Rice
authors.forename: J G
authors.initials: JG
authors.lastname: Supko
authors.forename: L
authors.initials: L
authors.lastname: Malspeis
authors.forename: R W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: D
authors.initials: D
authors.lastname: Clanton
authors.forename: M
authors.initials: M
authors.lastname: Bu
authors.forename: L
authors.initials: L
authors.lastname: Graham
authors.forename: C A
authors.initials: CA
authors.lastname: Schaeffer
authors.forename: J A
authors.initials: JA
authors.lastname: Turpin
authors.forename: J
authors.initials: J
authors.lastname: Domagala
authors.forename: R
authors.initials: R
authors.lastname: Gogliotti
authors.forename: J P
authors.initials: JP
authors.lastname: Bader
authors.forename: S M
authors.initials: SM
authors.lastname: Halliday
authors.forename: L
authors.initials: L
authors.lastname: Coren
authors.forename: R C
authors.initials: RC
authors.lastname: Sowder
authors.forename: L O
authors.initials: LO
authors.lastname: Arthur
authors.forename: L E
authors.initials: LE
authors.lastname: Henderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002213:Capsid / Q000737:chemistry / Q000378:metabolism*; D036022:Capsid Proteins; D002460:Cell Line; D004220:Disulfides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D015683:Gene Products, gag / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D014764:Viral Proteins; D016335:Zinc Fingers / Q000187:drug effects*; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D036022:Capsid Proteins; D004220:Disulfides; D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus