Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives' action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C70 derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C70 derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription-without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives' oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.
- MeSH
- fullereny metabolismus farmakologie MeSH
- genom virový účinky léků MeSH
- genové produkty gag - virus lidské imunodeficience metabolismus MeSH
- HEK293 buňky MeSH
- HIV-1 účinky léků genetika metabolismus fyziologie MeSH
- látky proti HIV metabolismus farmakologie MeSH
- lidé MeSH
- nukleokapsida - proteiny metabolismus MeSH
- reverzní transkripce MeSH
- RNA virová metabolismus MeSH
- svlékání virového obalu účinky léků MeSH
- vazba proteinů MeSH
- virion metabolismus MeSH
- zabalení virového genomu účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
