ArticleMolecules (Basel, Switzerland)2019
Field-Based Affinity Optimization of a Novel Azabicyclohexane Scaffold HIV-1 Entry Inhibitor.
Article in Molecules (Basel, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- Clade-Specific Alterations within the HIV-1 Capsid Protein with Implications for Nuclear Translocation.Biomolecules · 2022Article
- A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.Cell reports · 2020Article
- Composition and Orientation of the Core Region of Novel HIV-1 Entry Inhibitors Influences Metabolic Stability.Molecules (Basel, Switzerland) · 2020Article
- Bioisosteric Replacement as a Tool in Anti-HIV Drug Design.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Small-molecule HIV-1 entry inhibitors are an extremely attractive therapeutic modality. We have previously demonstrated that the entry inhibitor class can be optimized by using computational means to identify and extend the chemotypes available. Here we demonstrate unique and differential effects of previously published antiviral compounds on the gross structure of the HIV-1 Env complex, with an azabicyclohexane scaffolded inhibitor having a positive effect on glycoprotein thermostability. We demonstrate that modification of the methyltriazole-azaindole headgroup of these entry inhibitors directly effects the potency of the compounds, and substitution of the methyltriazole with an amine-oxadiazole increases the affinity of the compound 1000-fold over parental by improving the on-rate kinetic parameter. These findings support the continuing exploration of compounds that shift the conformational equilibrium of HIV-1 Env as a novel strategy to improve future inhibitor and vaccine design efforts.
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Registered trials
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