title: Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions.
abstract: BACKGROUND
  We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity.
  
  
  RESULTS
  KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while no inhibition of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to induce structural changes in gp41 normally associated with membrane fusion and cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades of HIV-1 as well as in fully infectious HIV-1 virions.
  
  
  CONCLUSIONS
  The antiviral activity of KR13 and its ability to inactivate virions prior to target cell engagement suggest that peptide triazole thiols could be highly effective in inhibiting HIV transmission across mucosal barriers and provide a novel probe to understand biochemical signals within envelope that are involved in membrane fusion.
authors: Arangassery Rosemary
authors: AR
authors: Bastian
authors: Mark
authors: M
authors: Contarino
authors: Lauren D
authors: LD
authors: Bailey
authors: Rachna
authors: R
authors: Aneja
authors: Diogo Rodrigo Magalhaes
authors: DR
authors: Moreira
authors: Kevin
authors: K
authors: Freedman
authors: Karyn
authors: K
authors: McFadden
authors: Caitlin
authors: C
authors: Duffy
authors: Ali
authors: A
authors: Emileh
authors: George
authors: G
authors: Leslie
authors: Jeffrey M
authors: JM
authors: Jacobson
authors: James A
authors: JA
authors: Hoxie
authors: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245N 15th Street, New College Building, Room No, 11102, Philadelphia, PA 19102, USA. ichaiken@drexelmed.edu.
authors: Irwin
authors: I
authors: Chaiken
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014230:Triazoles / Q000378:metabolism*; D014771:Virion / Q000187:drug effects*; D038301:Virus Inactivation
chemical_list: D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D010455:Peptides; D013438:Sulfhydryl Compounds; D014230:Triazoles; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1