ArticleProtein science : a publication of the Protein Society2012
Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors.
Article in Protein science : a publication of the Protein Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2.The Journal of infectious diseases · 2020Pooled it
- Evolution and emergence of the integrase inhibitor 231 insertion resistance mutation in an HIV-2 strain isolated in central Portugal.Virus genes · 2026Article
- Phenotypic impacts of treatment-selected mutations in HIV-2 protease on darunavir and lopinavir susceptibility: Evaluating genotypic HIV-2 drug resistance tools.PLOS global public health · 2026Article
- Development and characterization of high-affinity aptamers for HIV protease detection.Heliyon · 2024Article
- Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.Molecules (Basel, Switzerland) · 2023Article
- Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.International journal of molecular sciences · 2023Review
- High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients.International journal of molecular sciences · 2022Article
- Review
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Impacts of drug resistance mutations on the structural asymmetry of the HIV-2 protease.BMC molecular and cell biology · 2020Article
- Evaluation of 3-Dimensionality in Approved and Experimental Drug Space.ACS medicinal chemistry letters · 2020Article
- Proton transfer and drug binding details revealed in neutron diffraction studies of wild-type and drug resistant HIV-1 protease.Methods in enzymology · 2020Article
- Structural studies of antiviral inhibitor with HIV-1 protease bearing drug resistant substitutions of V32I, I47V and V82I.Biochemical and biophysical research communications · 2019Article
- Halogen Bond Interactions of Novel HIV-1 Protease Inhibitors (PI) (GRL-001-15 and GRL-003-15) with the Flap of Protease Are Critical for Their Potent Activity against Wild-Type HIV-1 and Multi-PI-Resistant Variants.Antimicrobial agents and chemotherapy · 2019Article
- The dawn of precision medicine in HIV: state of the art of pharmacotherapy.Expert opinion on pharmacotherapy · 2018Review
- Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.Scientific reports · 2018Article
- An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant.Journal of computer-aided molecular design · 2018Article
- Analysis of the HIV-2 protease's adaptation to various ligands: characterization of backbone asymmetry using a structural alphabet.Scientific reports · 2018Article
- Exploring the Reasons for Decrease in Binding Affinity of HIV-2 Against HIV-1 Protease Complex Using Interaction Entropy Under Polarized Force Field.Frontiers in chemistry · 2018Article
- Room Temperature Neutron Crystallography of Drug Resistant HIV-1 Protease Uncovers Limitations of X-ray Structural Analysis at 100 K.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR₂) than on HIV-1 protease (PR₁). We solved the crystal structure of PR₂ with APV at 1.5 Å resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR₁ mutant (PR(1M) ) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR₂. PR(1M) more closely resembled PR₂ than PR₁ in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR(1M) with APV, DRV, and SQV were compared with available PR₁ and PR₂ complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR(1M) and PR₁, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR(1M). Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR₁ (M) and PR₂ relative to the strong hydrogen bonds observed in PR₁, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR(1M) partially replicates the specificity of PR₂ and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.
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