ArticleBiochemistry2010
Physical trapping of HIV-1 synaptic complex by different structural classes of integrase strand transfer inhibitors.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Delineation of a novel assembly intermediate in Rous sarcoma virus integration pathway.Nucleic acids research · 2026Article
- Differential assembly of Rous sarcoma virus tetrameric and octameric intasomes is regulated by the C-terminal domain and tail region of integrase.The Journal of biological chemistry · 2018Article
- Recent advances in the discovery of small-molecule inhibitors of HIV-1 integrase.Future science OA · 2018Review
- A C-terminal "Tail" Region in the Rous Sarcoma Virus Integrase Provides High Plasticity of Functional Integrase Oligomerization during Intasome Assembly.The Journal of biological chemistry · 2017Article
- A targeted DNA substrate mechanism for the inhibition of HIV-1 integrase by inhibitors with antiretroviral activity.FEBS open bio · 2016Article
- Multifunctional facets of retrovirus integrase.World journal of biological chemistry · 2015Review
- Rous sarcoma virus synaptic complex capable of concerted integration is kinetically trapped by human immunodeficiency virus integrase strand transfer inhibitors.The Journal of biological chemistry · 2014Article
- Inhibiting the HIV integration process: past, present, and the future.Journal of medicinal chemistry · 2014Article
- Critical appraisal of elvitegravir in the treatment of HIV-1/AIDS.HIV/AIDS (Auckland, N.Z.) · 2014Review
- Effects of raltegravir on 2-long terminal repeat circle junctions in HIV type 1 viremic and aviremic patients.AIDS research and human retroviruses · 2013Article
- HIV Drug Resistance and the Advent of Integrase Inhibitors.Current infectious disease reports · 2013Article
- Novel therapeutic strategies targeting HIV integrase.BMC medicine · 2012Review
- First-in-class small molecule inhibitors of the single-strand DNA cytosine deaminase APOBEC3G.ACS chemical biology · 2012Article
- The Need for Development of New HIV-1 Reverse Transcriptase and Integrase Inhibitors in the Aftermath of Antiviral Drug Resistance.Scientifica · 2012Review
- Raltegravir in HIV-1 infection: Safety and Efficacy in Treatment-naïve Patients.Clinical medicine reviews in therapeutics · 2011Article
- The HIV-1 integrase monomer induces a specific interaction with LTR DNA for concerted integration.Biochemistry · 2011Article
- HIV-1 integrase strand transfer inhibitors stabilize an integrase-single blunt-ended DNA complex.Journal of molecular biology · 2011Article
- Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Raltegravir is an FDA approved inhibitor directed against human immunodeficiency virus type 1 (HIV-1) integrase (IN). In this study, we investigated the mechanisms associated with multiple strand transfer inhibitors capable of inhibiting concerted integration by HIV-1 IN. The results show raltegravir, elvitegravir, MK-2048, RDS 1997, and RDS 2197 all appear to encompass a common inhibitory mechanism by modifying IN-viral DNA interactions. These structurally different inhibitors bind to and inactivate the synaptic complex, an intermediate in the concerted integration pathway in vitro. The inhibitors physically trap the synaptic complex, thereby preventing target DNA binding and thus concerted integration. The efficiency of a particular inhibitor to trap the synaptic complex observed on native agarose gels correlated with its potency for inhibiting the concerted integration reaction, defined by IC(50) values for each inhibitor. At low nanomolar concentrations (<50 nM), raltegravir displayed a time-dependent inhibition of concerted integration, a property associated with slow-binding inhibitors. Studies of raltegravir-resistant IN mutants N155H and Q148H without inhibitors demonstrated that their capacity to assemble the synaptic complex and promote concerted integration was similar to their reported virus replication capacities. The concerted integration activity of Q148H showed a higher cross-resistance to raltegravir than observed with N155H, providing evidence as to why the Q148H pathway with secondary mutations is the predominant pathway upon prolonged treatment. Notably, MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H, suggesting this inhibitor may bind similarly within their drug-binding pockets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.