ArticleAntimicrobial agents and chemotherapy2014
Binding mode characterization of NBD series CD4-mimetic HIV-1 entry inhibitors by X-ray structure and resistance study.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 44 citations in OpenAlex.
- HIV envelope pseudotyped virus- an indispensable tool in HIV research.Virus research · 2026Review
- Soluble CD4 inhibits Ebola virus infection by targeting endosomal receptor-binding site.iScience · 2025Article
- V3 tip determinants of susceptibility to inhibition by CD4-mimetic compounds in natural clade A human immunodeficiency virus (HIV-1) envelope glycoproteins.Journal of virology · 2023Article
- Antiviral Activity and Crystal Structures of HIV-1 gp120 Antagonists.International journal of molecular sciences · 2022Article
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Characterization of Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Variants Selected for Resistance to a CD4-Mimetic Compound.Journal of virology · 2022Article
- Small-Molecule HIV Entry Inhibitors Targeting gp120 and gp41.Advances in experimental medicine and biology · 2022Review
- HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites.Journal of medicinal chemistry · 2021Article
- Design of gp120 HIV-1 entry inhibitors by scaffold hopping via isosteric replacements.European journal of medicinal chemistry · 2021Article
- Design, synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors.Current opinion in HIV and AIDS · 2020Review
- Synthesis of oxalamides by acceptorless dehydrogenative coupling of ethylene glycol and amines and the reverse hydrogenation catalyzed by ruthenium.Chemical science · 2020Article
- Article
- Preclinical Optimization of gp120 Entry Antagonists as anti-HIV-1 Agents with Improved Cytotoxicity and ADME Properties through Rational Design, Synthesis, and Antiviral Evaluation.Journal of medicinal chemistry · 2020Article
- Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1.Frontiers in pharmacology · 2020Article
- Strain-Dependent Activation and Inhibition of Human Immunodeficiency Virus Entry by a Specific PF-68742 Stereoisomer.Journal of virology · 2019Article
- In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4.Viruses · 2019Article
- Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor.Molecules (Basel, Switzerland) · 2018Article
- Synthesis, Antiviral Activity, and Structure-Activity Relationship of 1,3-Benzodioxolyl Pyrrole-Based Entry Inhibitors Targeting the Phe43 Cavity in HIV-1 gp120.ChemMedChem · 2018Article
- Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.European journal of medicinal chemistry · 2018Article
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 3 institutions in 1 country.
Funding
Abstract
We previously identified two small-molecule CD4 mimetics--NBD-556 and NBD-557--and synthesized a series of NBD compounds that resulted in improved neutralization activity in a single-cycle HIV-1 infectivity assay. For the current investigation, we selected several of the most active compounds and assessed their antiviral activity on a panel of 53 reference HIV-1 Env pseudoviruses representing diverse clades of clinical isolates. The selected compounds inhibited tested clades with low-micromolar potencies. Mechanism studies indicated that they act as CD4 agonists, a potentially unfavorable therapeutic trait, in that they can bind to the gp120 envelope glycoprotein and initiate a similar physiological response as CD4. However, one of the compounds, NBD-09027, exhibited reduced agonist properties, in both functional and biophysical studies. To understand the binding mode of these inhibitors, we first generated HIV-1-resistant mutants, assessed their behavior with NBD compounds, and determined the X-ray structures of two inhibitors, NBD-09027 and NBD-10007, in complex with the HIV-1 gp120 core at ∼2-Å resolution. Both studies confirmed that the NBD compounds bind similarly to NBD-556 and NBD-557 by inserting their hydrophobic groups into the Phe43 cavity of gp120. The basic nitrogen of the piperidine ring is located in close proximity to D368 of gp120 but it does not form any H-bond or salt bridge, a likely explanation for their nonoptimal antagonist properties. The results reveal the structural and biological character of the NBD series of CD4 mimetics and identify ways to reduce their agonist properties and convert them to antagonists.
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.