ArticleJournal of medicinal chemistry2013
Extreme multidrug resistant HIV-1 protease with 20 mutations is resistant to novel protease inhibitors with P1'-pyrrolidinone or P2-tris-tetrahydrofuran.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Design, Synthesis, and Biological Evaluation of Darunavir Analogs as HIV-1 Protease Inhibitors.ACS bio & med chem Au · 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
- Design and Evaluation of Novel HIV-1 Protease Inhibitors Containing Phenols or Polyphenols as P2 Ligands with High Activity against DRV-Resistant HIV-1 Variants.International journal of molecular sciences · 2022Article
- Joint neutron/molecular dynamics vibrational spectroscopy reveals softening of HIV-1 protease upon binding of a tight inhibitor.Physical chemistry chemical physics : PCCP · 2022Article
- Single-Agent and Fixed-Dose Combination HIV-1 Protease Inhibitor Drugs in Fission Yeast (Pathogens (Basel, Switzerland) · 2021Article
- Darunavir-Resistant HIV-1 Protease Constructs Uphold a Conformational Selection Hypothesis for Drug Resistance.Viruses · 2020Article
- Highly drug-resistant HIV-1 protease reveals decreased intra-subunit interactions due to clusters of mutations.The FEBS journal · 2020Article
- Novel HIV-1 Protease Inhibitors with Morpholine as the P2 Ligand to Enhance Activity against DRV-Resistant Variants.ACS medicinal chemistry letters · 2020Article
- Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20.Biochemical and biophysical research communications · 2019Article
- Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease.ACS infectious diseases · 2019Article
- Yeast for virus research.Microbial cell (Graz, Austria) · 2017Review
- A fission yeast cell-based system for multidrug resistant HIV-1 proteases.Cell & bioscience · 2017Article
- Effects of Hinge-region Natural Polymorphisms on Human Immunodeficiency Virus-Type 1 Protease Structure, Dynamics, and Drug Pressure Evolution.The Journal of biological chemistry · 2016Article
- Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS.Journal of medicinal chemistry · 2016Review
- Article
- Pulsed EPR characterization of HIV-1 protease conformational sampling and inhibitor-induced population shifts.Physical chemistry chemical physics : PCCP · 2016Article
- Article
- Substituted Bis-THF Protease Inhibitors with Improved Potency against Highly Resistant Mature HIV-1 Protease PR20.Journal of medicinal chemistry · 2015Article
- Highly resistant HIV-1 proteases and strategies for their inhibition.Future medicinal chemistry · 2015Review
- Prediction of HIV drug resistance from genotype with encoded three-dimensional protein structure.BMC genomics · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Extreme drug resistant mutant of HIV-1 protease (PR) bearing 20 mutations (PR20) has been studied with the clinical inhibitor amprenavir (1) and two potent antiviral investigational inhibitors GRL-02031 (2) and GRL-0519 (3). Clinical inhibitors are >1000-fold less active on PR20 than on wild-type enzyme, which is consistent with dissociation constants (KL) from isothermal titration calorimetry of 40 nM for 3, 178 nM for amprenavir, and 960 nM for 2. High resolution crystal structures of PR20-inhibitor complexes revealed altered interactions compared with the corresponding wild-type PR complexes in agreement with relative inhibition. Amprenavir lacks interactions due to PR20 mutations in the S2/S2' subsites relative to PR. Inhibitors 2 and 3 lose interactions with Arg8' in PR20 relative to the wild-type enzyme because Arg8' shifts to interact with mutated L10F side chain. Overall, inhibitor 3 compares favorably with darunavir in affinity for PR20 and shows promise for further development.
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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.