ArticleCurrent opinion in HIV and AIDS2008
New approaches to HIV protease inhibitor drug design II: testing the substrate envelope hypothesis to avoid drug resistance and discover robust inhibitors.
Article in Current opinion in HIV and AIDS, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Exploring evolutionary trajectories of drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Contributions of Hyperactive Mutations in MACS infectious diseases · 2024Article
- Article
- Prediction of HIV-1 protease cleavage site from octapeptide sequence information using selected classifiers and hybrid descriptors.BMC bioinformatics · 2022Article
- A synergy of activity, stability, and inhibitor-interaction of HIV-1 protease mutants evolved under drug-pressure.Protein science : a publication of the Protein Society · 2021Article
- Probing the Interaction between HIV-1 Protease and the Homodimeric p66/p66' Reverse Transcriptase Precursor by Double Electron-Electron Resonance EPR Spectroscopy.Chembiochem : a European journal of chemical biology · 2020Article
- NMR and MD studies combined to elucidate inhibitor and water interactions of HIV-1 protease and their modulations with resistance mutations.Journal of biomolecular NMR · 2019Article
- Characterizing early drug resistance-related events using geometric ensembles from HIV protease dynamics.Scientific reports · 2018Article
- Interdependence of Inhibitor Recognition in HIV-1 Protease.Journal of chemical theory and computation · 2017Article
- Improving Viral Protease Inhibitors to Counter Drug Resistance.Trends in microbiology · 2016Review
- The importance of physicochemical characteristics and nonlinear classifiers in determining HIV-1 protease specificity.Bioengineered · 2016Article
- Pulsed EPR characterization of HIV-1 protease conformational sampling and inhibitor-induced population shifts.Physical chemistry chemical physics : PCCP · 2016Article
- Elucidation of the Molecular Mechanism Driving Duplication of the HIV-1 PTAP Late Domain.Journal of virology · 2016Article
- The Glucose Transporter PfHT1 Is an Antimalarial Target of the HIV Protease Inhibitor Lopinavir.Antimicrobial agents and chemotherapy · 2015Article
- A virtual screen discovers novel, fragment-sized inhibitors of Mycobacterium tuberculosis InhA.Journal of chemical information and modeling · 2015Article
- Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution.Evolutionary applications · 2015Article
- Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.Chemistry & biology · 2013Article
- Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The challenge of developing robust drugs to overcome resistance.Drug discovery today · 2011Article
- Dynamics of preferential substrate recognition in HIV-1 protease: redefining the substrate envelope.Journal of molecular biology · 2011Article
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2 authors.
Funding
Abstract
purpose of reviewDrug resistance results when the balance between the binding of inhibitors and the turnover of substrates is perturbed in favor of the substrates. Resistance is quite widespread to the HIV-1 protease inhibitors permitting the protease to process its 10 different substrates. This processing of the substrates permits the virus HIV-1 to mature and become infectious. The design of HIV-1 protease inhibitors that closely fit within the substrate-binding region is proposed to be a strategy to avoid drug resistance. RECENT
findingsCocrystal structures of HIV-1 protease with its substrates define an overlapping substrate-binding region or substrate envelope. Novel HIV-1 protease inhibitors that were designed to fit within this substrate envelope were found to retain high binding affinity and have a flat binding profile against a panel of drug-resistant HIV-1 proteases. SUMMARY: The avoidance of drug resistance needs to be considered in the initial design of inhibitors to quickly evolving targets such as HIV-1 protease. Using a detailed knowledge of substrate binding appears to be a promising strategy for achieving this goal to obtain robust HIV-1 protease inhibitors.
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