title: Aspirin-like molecules that inhibit human immunodeficiency virus 1 replication.
abstract: Some anti-inflammatory molecules are also known to possess anti-human immunodeficiency virus (HIV) activity. We found that o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS), a recently synthesized non-steroidal anti-inflammatory molecule can inhibit HIV-1 replication. The aim of this study was to clarify the mechanism of action of APHS. When administered during the first steps of the infection, APHS was capable of inhibiting the replication of several HIV-1 strains (macrophage-tropic and/or lymphocytotropic) in a dose-dependent manner in both peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages and peripheral blood lymphocytes with 50% inhibitory concentration values of approximately 10 microM. The 50% toxic concentration of APHS varied between 100 and 200 microM in the different primary cells tested. APHS did not affect HIV-1 replication once the provirus was already inserted into the cellular genome. APHS also did not inhibit HIV-1 entry into the host cells as determined by quantification of gag RNA inside PBMC 2h after infection. However, APHS did inhibit gag DNA synthesis during reverse transcription in primary cells, which indicates that APHS may target the reverse transcription process.
authors.affiliation: Eijkman-Winkler Center, HpG04.614, University Medical Center Utrecht, Heidelberglaan 100, NL-3584, CX Utrecht, The Netherlands. c.f.pereira@lab.azu.nl
authors.forename: Cândida F
authors.initials: CF
authors.lastname: Pereira
authors.forename: Judith T M L
authors.initials: JT
authors.lastname: Paridaen
authors.forename: Karla
authors.initials: K
authors.lastname: Rutten
authors.forename: Marleen C D G
authors.initials: MC
authors.lastname: Huigen
authors.forename: Marja
authors.initials: M
authors.lastname: van de Bovenkamp
authors.forename: Jeena
authors.initials: J
authors.lastname: Middel
authors.forename: Nancy
authors.initials: N
authors.lastname: Beerens
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: Jan
authors.initials: J
authors.lastname: Verhoef
authors.forename: Hans S L M
authors.initials: HS
authors.lastname: Nottet
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000821:virology; D009000:Monocytes / Q000821:virology; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D019914:Taq Polymerase / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004279:DNA, Viral; D012367:RNA, Viral; D013440:Sulfides; C112390:o-(acetoxyphenyl)hept-2-ynyl sulfide; D019914:Taq Polymerase; D000114:Acetylene; D001241:Aspirin