ArticleJournal of virology2010
A low-molecular-weight entry inhibitor of both CCR5- and CXCR4-tropic strains of human immunodeficiency virus type 1 targets a novel site on gp41.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Multiplexed Epitope Mapping of HIV-1 Neutralizing Antibodies by Coupling Chemical Labeling of Cysteines to Deep Sequencing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Review
- Virus Entry Inhibitors: Past, Present, and Future.Advances in experimental medicine and biology · 2022Review
- A facile method of mapping HIV-1 neutralizing epitopes using chemically masked cysteines and deep sequencing.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Strain-Dependent Activation and Inhibition of Human Immunodeficiency Virus Entry by a Specific PF-68742 Stereoisomer.Journal of virology · 2019Article
- Functional Stability of HIV-1 Envelope Trimer Affects Accessibility to Broadly Neutralizing Antibodies at Its Apex.Journal of virology · 2017Article
- High-Throughput HIV-Cell Fusion Assay for Discovery of Virus Entry Inhibitors.Assay and drug development technologies · 2015Article
- Current progress in antiviral strategies.Trends in pharmacological sciences · 2014Review
- Development of a rapid cell-fusion-based phenotypic HIV-1 tropism assay.Journal of the International AIDS Society · 2013Article
- Increased functional stability and homogeneity of viral envelope spikes through directed evolution.PLoS pathogens · 2013Article
- Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity.PLoS pathogens · 2013Article
- HIV-1 fusion is blocked through binding of GB Virus C E2-derived peptides to the HIV-1 gp41 disulfide loop [corrected].PloS one · 2013Article
- Review
- Domain flexibility modulates the heterogeneous assembly mechanism of anthrax toxin protective antigen.Journal of molecular biology · 2012Article
- G protein-coupled receptors--recent advances.Acta biochimica Polonica · 2012Review
- Amphipathic properties of HIV-1 gp41 fusion inhibitors.Current topics in medicinal chemistry · 2011Review
- Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.Current topics in medicinal chemistry · 2011Review
- Article
- Chemokine receptor CCR5: from AIDS to atherosclerosis.British journal of pharmacology · 2011Review
- An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors.PloS one · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
A low-molecular-weight human immunodeficiency virus type 1 (HIV-1) inhibitor, PF-68742 (molecular weight, 573), has been identified in a high-throughput screen for compounds that block HIV-1 envelope glycoprotein (Env)-mediated fusion. The compound is shown to be potent against R5 and X4 isolates in both cell-cell fusion and antiviral assays (50% effective concentrations of approximately 0.1 to 1 muM). Postfusion and HIV-1 pseudotyping control experiments confirm that PF-68742 is an entry inhibitor with Env as the specific target for antiviral action. PF-68742 was not able to block binding of monomeric gp120 to soluble CD4 or the binding of gp120:CD4 complexes to cell-associated CCR5, thus distinguishing PF-68742 from described gp120 antagonists and coreceptor binders. Escape variants of HIV-1(NL4-3) were selected, and all resistant viruses were found to contain a common G514R (HxB2 numbering) mutation in Env, located proximal to the furin cleavage site in the fusion peptide of gp41. When introduced into wild-type NL4-3 gp41, G514R conferred resistance to PF-68742. Resistance via G514R is shown to be associated with enhancement of virion infectivity by PF-68742 that may result from altered properties of inhibitor-bound Env, rather than from a loss of compound binding. Wild-type viruses and those with substitutions in the disulfide loop (DSL) region of gp41 were also examined for PF-68742 sensitivity. Here, complete resistance to PF-68742 was found to occur through changes outside of position 514, including in the gp41 DSL region. The results highlight PF-68742 as a starting point for novel therapies against HIV-1 and provide new insights into models of Env-mediated fusion.
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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.