Aspirin-like molecules that inhibit human immunodeficiency virus 1 replication

Cândida F Pereira, Judith T M L Paridaen, Karla Rutten, Marleen C D G Huigen, Marja van de Bovenkamp, Jeena Middel, Nancy Beerens, Ben Berkhout, Rob Schuurman, Lawrence J Marnett, Jan Verhoef, Hans S L M Nottet

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)253-63
Number of pages11
JournalAntiviral Research
Volume58
Issue number3
DOIs
Publication statusPublished - May-2003
Externally publishedYes

Keywords

  • Acetylene
  • Alkynes
  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin
  • Cell Line
  • Cells, Cultured
  • DNA, Viral
  • HIV-1
  • Humans
  • Leukocytes, Mononuclear
  • Lymphocytes
  • Macrophages
  • Monocytes
  • Polymerase Chain Reaction
  • RNA, Viral
  • Sulfides
  • Taq Polymerase
  • Transcription, Genetic
  • Virus Replication
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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