ArticleJournal of medicinal chemistry2013
Novel P2 tris-tetrahydrofuran group in antiviral compound 1 (GRL-0519) fills the S2 binding pocket of selected mutants of HIV-1 protease.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Advancements in development of novel class of HIV protease inhibitors.Annals of medicine · 2026Review
- Recent Advances in Heterocyclic HIV Protease Inhibitors.International journal of molecular sciences · 2025Review
- Exploring the potential of some natural indoles as antiviral agents: quantum chemical analysis, inverse molecular docking, and affinity calculations.Frontiers in chemistry · 2024Article
- HIV-1 protease with 10 lopinavir and darunavir resistance mutations exhibits altered inhibition, structural rearrangements and extreme dynamics.Journal of molecular graphics & modelling · 2022Article
- Phosphine-catalyzed divergent domino processes between γ-substituted allenoates and carbonyl-activated alkenes.Chemical science · 2022Article
- The Pseudo-SymmetricBiomolecules · 2021Article
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.Biochemical and biophysical research communications · 2019Article
- Beyond Members of theAntimicrobial agents and chemotherapy · 2019Article
- Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease.ACS omega · 2018Article
- Probing Lipophilic Adamantyl Group as the P1-Ligand for HIV-1 Protease Inhibitors: Design, Synthesis, Protein X-ray Structural Studies, and Biological Evaluation.Journal of medicinal chemistry · 2016Article
- Computational Studies of a Mechanism for Binding and Drug Resistance in the Wild Type and Four Mutations of HIV-1 Protease with a GRL-0519 Inhibitor.International journal of molecular sciences · 2016Article
- Design of new potent HTLV-1 protease inhibitors: in silico study.Molecular biology research communications · 2016Article
- Structure-based design of potent HIV-1 protease inhibitors with modified P1-biphenyl ligands: synthesis, biological evaluation, and enzyme-inhibitor X-ray structural studies.Journal of medicinal chemistry · 2015Article
- Enantioselective Synthesis of Dioxatriquinane Structural Motifs for HIV-1 Protease Inhibitors Using a Cascade Radical Cyclization.Tetrahedron letters · 2015Article
- Aureonitol, a Fungi-Derived Tetrahydrofuran, Inhibits Influenza Replication by Targeting Its Surface Glycoprotein Hemagglutinin.PloS one · 2015Article
- Highly resistant HIV-1 proteases and strategies for their inhibition.Future medicinal chemistry · 2015Review
- Structures of darunavir-resistant HIV-1 protease mutant reveal atypical binding of darunavir to wide open flaps.ACS chemical biology · 2014Article
- Highly potent HIV-1 protease inhibitors with novel tricyclic P2 ligands: design, synthesis, and protein-ligand X-ray studies.Journal of medicinal chemistry · 2013Article
- Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design.Journal of medicinal chemistry · 2013Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
GRL-0519 (1) is a potent antiviral inhibitor of HIV-1 protease (PR) possessing tris-tetrahydrofuran (tris-THF) at P2. The high resolution X-ray crystal structures of inhibitor 1 in complexes with single substitution mutants PR(R8Q), PR(D30N), PR(I50V), PR(I54M), and PR(V82A) were analyzed in relation to kinetic data. The smaller valine side chain in PR(I50V) eliminated hydrophobic interactions with inhibitor and the other subunit consistent with 60-fold worse inhibition. Asn30 in PR(D30N) showed altered interactions with neighboring residues and 18-fold worse inhibition. Mutations V82A and I54M showed compensating structural changes consistent with 6-7-fold lower inhibition. Gln8 in PR(R8Q) replaced the ionic interactions of wild type Arg8 with hydrogen bond interactions without changing the inhibition significantly. The carbonyl oxygen of Gly48 showed two alternative conformations in all structures likely due to the snug fit of the large tris-THF group in the S2 subsite in agreement with high antiviral efficacy of 1 on resistant virus.
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