ArticleThe Journal of biological chemistry2012
Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
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Who cites it
119 citing papers in PubMed, 177 citations in OpenAlex.
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Mapping the TAR vRNA Interaction with HIV-1 Integrase.Viruses · 2026Article
- Mapping the vRNA Interaction with HIV-1 Integrase.bioRxiv : the preprint server for biology · 2026Article
- 2-(Trihydroxyphenyl)thienopyrimidinones as Key Scaffolds for Targeting a Novel Allosteric Site of HIV-1 Integrase.Molecules (Basel, Switzerland) · 2025Article
- Retrointegration2023-Papers from the 7th International Conference on Retroviral Integration.Viruses · 2025Article
- Article
- Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2.Biophysical journal · 2024Article
- Optimizing the Multimerization Properties of Quinoline-Based Allosteric HIV-1 Integrase Inhibitors.Viruses · 2024Review
- The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir.bioRxiv : the preprint server for biology · 2024Article
- Dihydroxyphenyl- and Heteroaromatic-Based Thienopyrimidinones to Tackle HIV-1 LEDGF/p75-Dependent IN Activity.Molecules (Basel, Switzerland) · 2023Article
- HIV-1 Integrase Inhibition Activity by Spiroketals Derived fromPharmaceuticals (Basel, Switzerland) · 2023Article
- Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase.Antimicrobial agents and chemotherapy · 2023Article
- GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture.Antimicrobial agents and chemotherapy · 2023Article
- Structure of a HIV-1 IN-Allosteric inhibitor complex at 2.93 Å resolution: Routes to inhibitor optimization.PLoS pathogens · 2023Article
- The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function.mBio · 2023Article
- 5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action.Frontiers in cellular and infection microbiology · 2023Article
- Article
- Article
- Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors.Viruses · 2022Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The multifunctional HIV-1 enzyme integrase interacts with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript into a host cell chromosome. These interactions are crucial for HIV-1 replication and present attractive targets for antiviral therapy. Recently, 2-(quinolin-3-yl) acetic acid derivatives were reported to selectively inhibit the integrase-LEDGF interaction in vitro and impair HIV-1 replication in infected cells. Here, we show that this class of compounds impairs both integrase-LEDGF binding and LEDGF-independent integrase catalytic activities with similar IC(50) values, defining them as bona fide allosteric inhibitors of integrase function. Furthermore, we show that 2-(quinolin-3-yl) acetic acid derivatives block the formation of the stable synaptic complex between integrase and viral DNA by allosterically stabilizing an inactive multimeric form of integrase. In addition, these compounds inhibit LEDGF binding to the stable synaptic complex. This multimode mechanism of action concordantly results in cooperative inhibition of the concerted integration of viral DNA ends in vitro and HIV-1 replication in cell culture. Our findings, coupled with the fact that high cooperativity of antiviral inhibitors correlates with their increased instantaneous inhibitory potential, an important clinical parameter, argue strongly that improved 2-(quinolin-3-yl) acetic acid derivatives could exhibit desirable clinical properties.
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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.