Effect of nucleoside analogs and non-nucleoside inhibitors of HIV-1 reverse transcriptase on cell-free virions
| Autor: | H. J. A. Fleury, Laura Tarrago-Litvak, Simon Litvak, Valerie Dolle, Chi Hung Nguyen, Michel Ventura, Michel Legraverend |
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| Rok vydání: | 1999 |
| Předmět: |
Infectivity
Nucleoside analogue biology Anti-HIV Agents Virion Nucleosides General Medicine biology.organism_classification Nucleotidyltransferase Virology Molecular biology Reverse transcriptase Virus HIV Reverse Transcriptase Enzyme inhibitor Lentivirus medicine biology.protein HIV-1 Humans Reverse Transcriptase Inhibitors Nucleoside medicine.drug Cell Line Transformed |
| Zdroj: | Archives of virology. 144(3) |
| ISSN: | 0304-8608 |
| Popis: | Reverse transcription takes place in the cytoplasm of infected cells, although it has been demonstrated that retroviruses can also initiate reverse transcription prior to infection of target cells. In addition to partial reverse transcripts, full-length proviral molecules have been detected in the plasma and seminal fluid of HIV-1 seropositive patients. Intravirion endogenous reverse transcription appears to be directly correlated with an increased level of infectivity. Therefore, the ability of an inhibitor to reach and inhibit the replication complex in the core of the free-virion may constitute an important part of its capacity to suppress viral infection. In this work we tested the ability of some reverse transcriptase inhibitors to decrease viral infectivity in pretreated highly purified virions. Our results showed that Curie pyridinone [Dolle et al. (1995), J Med Chem 38: 4 679–4 686], a non nucleoside RT inhibitor, strongly inhibited the infectivity of extracellular HIV-1 particles. Other non nucleoside inhibitors (TIBO R82913, HEPT, nevirapine) tested in these conditions were unable to do so. Our data indicate that the effect of Curie pyridinone on intact virions may be related to its capacity to tightly bind the target RT. This approach may lead to the design and synthesis of new drugs able to interact with the retroviral enzyme inside the viral core. |
| Databáze: | OpenAIRE |
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