Small molecule inhibitor of HIV-1 nuclear import suppresses HIV-1 replication in human lymphoid tissue ex vivo: a potential addition to current anti-HIV drug repertoire.
Despite recent progress in anti-HIV therapy, which has to do mainly with introduction of protease inhibitors into clinical practice, drug toxicity and emergence of drug-resistant isolates during the long-term treatment of the patients necessitates search for new drugs that can be added to currently used components of a multi-drug cocktail in highly active anti-retroviral therapy (HAART). Recently, we described a class of arylene bis(methylketone) compounds that inhibit nuclear import of HIV-1 pre-integration complexes and suppress viral replication in macrophages and PBMC in vitro. In this report, we demonstrate that one of these compounds, CNI-H1194, inhibited HIV-1 replication in primary lymphoid tissue ex vivo. The compound did not antagonize the activity of currently used anti-HIV drugs that inhibit viral reverse transcriptase or protease. These results suggest that arylene bis(methylketone) compounds might be a valuable addition to HAART.
Glushakova
S
S
The Laboratory of Cellular and Molecular Biophysics, NICHD, NIH, Bethesda, MD 20892, USA.
Dubrovsky
L
L
Grivel
J
J
Haffar
O
O
Bukrinsky
M
M
D000814:Aniline Compounds / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018929:Cell Culture Techniques; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000821:virology; D019888:Nelfinavir / Q000494:pharmacology; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000276:immunology / Q000821:virology*; D011743:Pyrimidines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000814:Aniline Compounds; D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C106925:CNI H1194; D015215:Zidovudine; D019888:Nelfinavir