ArticleProceedings of the National Academy of Sciences of the United States of America2008
Highly potent, fully recombinant anti-HIV chemokines: reengineering a low-cost microbicide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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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.
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Who cites it
78 citing papers in PubMed, 141 citations in OpenAlex.
- Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Traffic control: Mechanisms of ligand-specific internalization and intracellular distribution of CCR5.Molecular pharmacology · 2025Article
- Efficient production of fluorophore-labeled CC chemokines for biophysical studies using recombinant enterokinase and recombinant sortase.Biopolymers · 2024Article
- Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions.Scientific reports · 2024Article
- Rational Engineering of a Sub-Picomolar HIV-1 Blocker.Viruses · 2022Article
- Novel small synthetic HIV-1 V3 crown variants: CCR5 targeting ligands.Journal of biochemistry · 2022Article
- Filling the Gaps in Antagonist CCR5 Binding, a Retrospective and Perspective Analysis.Frontiers in immunology · 2022Article
- Endogenous Peptide Inhibitors of HIV Entry.Advances in experimental medicine and biology · 2022Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5.Nature communications · 2021Article
- Purinergic Receptors Crosstalk with CCR5 to Amplify CaCellular and molecular neurobiology · 2021Article
- Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist.Science advances · 2021Article
- Functional anatomy of the full-length CXCR4-CXCL12 complex systematically dissected by quantitative model-guided mutagenesis.Science signaling · 2020Article
- Selective Allosteric Modulation of N-Terminally Cleaved, but Not Full Length CCL3 in CCR1.ACS pharmacology & translational science · 2019Article
- Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders.Cellular and molecular life sciences : CMLS · 2019Review
- High-Affinity Binding of Chemokine Analogs that Display Ligand Bias at the HIV-1 Coreceptor CCR5.Biophysical journal · 2019Article
- Sustained release silk fibroin discs: Antibody and protein delivery for HIV prevention.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Rapid and low-cost multiplex synthesis of chemokine analogs.The Journal of biological chemistry · 2018Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
New prevention strategies for use in developing countries are urgently needed to curb the worldwide HIV/AIDS epidemic. The N-terminally modified chemokine PSC-RANTES is a highly potent entry inhibitor against R5-tropic HIV-1 strains, with an inhibitory mechanism involving long-term intracellular sequestration of the HIV coreceptor, CCR5. PSC-RANTES is fully protective when applied topically in a macaque model of vaginal HIV transmission, but it has 2 potential disadvantages related to further development: the requirement for chemical synthesis adds to production costs, and its strong CCR5 agonist activity might induce local inflammation. It would thus be preferable to find a recombinant analogue that retained the high potency of PSC-RANTES but lacked its agonist activity. Using a strategy based on phage display, we set out to discover PSC-RANTES analogs that contain only natural amino acids. We sought molecules that retain the potency and inhibitory mechanism of PSC-RANTES, while trying to reduce CCR5 signaling to as low a level as possible. We identified 3 analogues, all of which exhibit in vitro potency against HIV-1 comparable to that of PSC-RANTES. The first, 6P4-RANTES, resembles PSC-RANTES in that it is a strong agonist that induces prolonged intracellular sequestration of CCR5. The second, 5P12-RANTES, has no detectable G protein-linked signaling activity and does not bring about receptor sequestration. The third, 5P14-RANTES, induces significant levels of CCR5 internalization without detectable G protein-linked signaling activity. These 3 molecules represent promising candidates for further development as topical HIV prevention strategies.
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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.