ArticleThe Journal of biological chemistry2011
New insights into the mechanisms whereby low molecular weight CCR5 ligands inhibit HIV-1 infection.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial.BMC neurology · 2024Trial
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- CCR5 as a Therapeutic Target in HIV Disease: From CRISPR/Cas9 Gene Editing to Maraviroc-Mediated Inhibition.Viruses · 2026Review
- Coreceptor usage of plasma and cerebrospinal fluid-derived HIV-1 subtype C variants.Virology journal · 2026Article
- Asthma-mediated control of optic glioma growth via T cell-microglia interactions: A mathematical model.NPJ systems biology and applications · 2026Article
- Targeting of specific CCR5-G protein complexes underlies biased signaling by HIV-1 envelope glycoproteins.Cell communication and signaling : CCS · 2025Article
- High concentrations of Maraviroc do not alter immunological and metabolic parameters of CD4 T cells.Scientific reports · 2024Article
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- Development of tolerance to chemokine receptor antagonists: current paradigms and the need for further investigation.Frontiers in immunology · 2023Review
- Article
- HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages.PLoS pathogens · 2022Article
- How Do Modulators Affect the Orthosteric and Allosteric Binding Pockets?ACS chemical neuroscience · 2022Article
- Computational study of the structural ensemble of CC chemokine receptor type 5 (CCR5) and its interactions with different ligands.PloS one · 2022Article
- Modeling of CCR5 Recognition by HIV-1 gp120: How the Viral Protein Exploits the Conformational Plasticity of the Coreceptor.Viruses · 2021Article
- Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.Frontiers in immunology · 2021Article
- Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound.Scientific reports · 2020Article
- Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.Virulence · 2020Review
- Inhibitory Effect of PIK-24 on Respiratory Syncytial Virus Entry by Blocking Phosphatidylinositol-3 Kinase Signaling.Antimicrobial agents and chemotherapy · 2020Article
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 2020Review
- The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3).International journal of molecular sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CC chemokine receptor 5 (CCR5) is a G-protein-coupled receptor for the chemokines CCL3, -4, and -5 and a coreceptor for entry of R5-tropic strains of human immunodeficiency virus type 1 (HIV-1) into CD4(+) T-cells. We investigated the mechanisms whereby nonpeptidic, low molecular weight CCR5 ligands block HIV-1 entry and infection. Displacement binding assays and dissociation kinetics demonstrated that two of these molecules, i.e. TAK779 and maraviroc (MVC), inhibit CCL3 and the HIV-1 envelope glycoprotein gp120 binding to CCR5 by a noncompetitive and allosteric mechanism, supporting the view that they bind to regions of CCR5 distinct from the gp120- and CCL3-binding sites. We observed that TAK779 and MVC are full and weak inverse agonists for CCR5, respectively, indicating that they stabilize distinct CCR5 conformations with impaired abilities to activate G-proteins. Dissociation of [(125)I]CCL3 from CCR5 was accelerated by TAK779, to a lesser extent by MVC, and by GTP analogs, suggesting that inverse agonism contributes to allosteric inhibition of the chemokine binding to CCR5. TAK779 and MVC also promote dissociation of [(35)S]gp120 from CCR5 with an efficiency that correlates with their ability to act as inverse agonists. Displacement experiments revealed that affinities of MVC and TAK779 for the [(35)S]gp120-binding receptors are in the same range (IC(50) ∼6.4 versus 22 nm), although we found that MVC is 100-fold more potent than TAK779 for inhibiting HIV infection. This suggests that allosteric CCR5 inhibitors not only act by blocking gp120 binding but also alter distinct steps of CCR5 usage in the course of HIV infection.
Indexed as
Identifiers
What OpenQuestion holds
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.