ArticleJournal of medicinal chemistry2014
An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild-type and drug-resistant proteases.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Conformational asymmetry of human immunodeficiency virus-1 protease flaps increases along the darunavir drug resistance pathway.Protein science : a publication of the Protein Society · 2026Article
- Subtype-Specific HIV-1 Protease and the Role of Hinge and Flap Dynamics in Drug Resistance: A Subtype C Narrative.Viruses · 2025Review
- The structural, dynamic, and thermodynamic basis of darunavir resistance of a heavily mutated HIV-1 protease using molecular dynamics simulation.Frontiers in molecular biosciences · 2022Article
- Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022Article
- Molecular Docking-Based Screening for Novel Inhibitors of the Human Immunodeficiency Virus Type 1 Protease that Effectively Reduce the Viral Replication in Human Cells.Journal of AIDS & clinical research · 2021Article
- Benzothiazoles as potential antiviral agents.The Journal of pharmacy and pharmacology · 2020Review
- The Determination of HIV-1 RT Mutation Rate, Its Possible Allosteric Effects, and Its Implications on Drug Resistance.Viruses · 2020Review
- Flap-site Fragment Restores Back Wild-type Behaviour in Resistant Form of HIV Protease.Molecular informatics · 2018Article
- Unprecedented selective homogeneous cobalt-catalysed reductive alkoxylation of cyclic imides under mild conditions.Chemical science · 2017Article
- A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.PLoS pathogens · 2017Article
- Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.Journal of medicinal chemistry · 2016Review
- Role of Conformational Motions in Enzyme Function: Selected Methodologies and Case Studies.Catalysts (Basel, Switzerland) · 2016Article
- DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites.Journal of medicinal chemistry · 2016Article
- Identifying binding hot spots on protein surfaces by mixed-solvent molecular dynamics: HIV-1 protease as a test case.Biopolymers · 2016Article
- Selective Targeting of Cells via Bispecific Molecules That Exploit Coexpression of Two Intracellular Proteins.ACS chemical biology · 2015Article
- A Direct Interaction with RNA Dramatically Enhances the Catalytic Activity of the HIV-1 Protease In Vitro.Journal of molecular biology · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
NMR and MD simulations have demonstrated that the flaps of HIV-1 protease (HIV-1p) adopt a range of conformations that are coupled with its enzymatic activity. Previously, a model was created for an allosteric site located between the flap and the core of HIV-1p, called the Eye site (Biopolymers 2008, 89, 643-652). Here, results from our first study were combined with a ligand-based, lead-hopping method to identify a novel compound (NIT). NIT inhibits HIV-1p, independent of the presence of an active-site inhibitor such as pepstatin A. Assays showed that NIT acts on an allosteric site other than the dimerization interface. MD simulations of the ligand-protein complex show that NIT stably binds in the Eye site and restricts the flaps. That bound state of NIT is consistent with a crystal structure of similar fragments bound in the Eye site (Chem. Biol. Drug Des. 2010, 75, 257-268). Most importantly, NIT is equally potent against wild-type and a multidrug-resistant mutant of HIV-1p, which highlights the promise of allosteric inhibitors circumventing existing clinical resistance.
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Registered trials
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