ArticleNucleic acids research2011
Identification of a methylated oligoribonucleotide as a potent inhibitor of HIV-1 reverse transcription complex.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- A mutant tat protein inhibits HIV-1 reverse transcription by targeting the reverse transcription complex.Journal of virology · 2015Article
- Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1.Current topics in microbiology and immunology · 2015Review
- Advances in targeting nucleocapsid-nucleic acid interactions in HIV-1 therapy.Virus research · 2014Review
- Retrospective on the all-in-one retroviral nucleocapsid protein.Virus research · 2014Review
- Site-selective probing of cTAR destabilization highlights the necessary plasticity of the HIV-1 nucleocapsid protein to chaperone the first strand transfer.Nucleic acids research · 2013Article
- Zinc finger function of HIV-1 nucleocapsid protein is required for removal of 5'-terminal genomic RNA fragments: a paradigm for RNA removal reactions in HIV-1 reverse transcription.Virus research · 2013Article
- Identification of a minimal region of the HIV-1 5'-leader required for RNA dimerization, NC binding, and packaging.Journal of molecular biology · 2012Article
- Characterization of the inhibition mechanism of HIV-1 nucleocapsid protein chaperone activities by methylated oligoribonucleotides.Antimicrobial agents and chemotherapy · 2012Article
- Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides.Nucleic acids research · 2011Article
- Jean-Luc Darlix: Renaissance scientist and retrovirologist par excellence.Retrovirology · 2011Article
- Rapid titration of measles and other viruses: optimization with determination of replication cycle length.PloS one · 2011Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon HIV-1 infection of a target cell, the viral reverse transcriptase (RT) copies the genomic RNA to synthesize the viral DNA. The genomic RNA is within the incoming HIV-1 core where it is coated by molecules of nucleocapsid (NC) protein that chaperones the reverse transcription process. Indeed, the RT chaperoning properties of NC extend from the initiation of cDNA synthesis to completion of the viral DNA. New and effective drugs against HIV-1 continue to be required, which prompted us to search for compounds aimed at inhibiting NC protein. Here, we report that the NC chaperoning activity is extensively inhibited in vitro by small methylated oligoribonucleotides (mODN). These mODNs were delivered intracellularly using a cell-penetrating-peptide and found to impede HIV-1 replication in primary human cells at nanomolar concentrations. Extensive analysis showed that viral cDNA synthesis was severely impaired by mODNs. Partially resistant viruses with mutations in NC and RT emerged after months of passaging in cell culture. A HIV-1 molecular clone (NL4.3) bearing these mutations was found to replicate at high concentrations of mODN, albeit with a reduced fitness. Small, methylated ODNs such as mODN-11 appear to be a new type of highly potent inhibitor of HIV-1.
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Registered trials
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