ArticleChemistry & biology2013
Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- The substrate envelope strategy: Structural basis for resistance mitigation in antiviral drug design.Pharmaceutical science advances · 2026Review
- A Dynamics-Informed Machine Learning Framework for Inhibitor Optimization Against Quickly Evolving Targets to Avoid Resistance.bioRxiv : the preprint server for biology · 2026Article
- 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
- Fluorinated HIV-1 protease inhibitors containing chiral hydroxyethylbenzene and indanol as P2' ligands with potent activity against drug-resistant variants.European journal of medicinal chemistry · 2026Article
- Potential of Boronic Acid Derivatization and Activity in Agrochemical Discovery.Molecules (Basel, Switzerland) · 2025Review
- Article
- Elucidating the Substrate Envelope of Enterovirus 68-3C Protease: Structural Basis of Specificity and Potential Resistance.Viruses · 2024Article
- The human retroviral-like aspartic protease 1 (ASPRV1): From in vitro studies to clinical correlations.The Journal of biological chemistry · 2024Review
- Interplay between protease and reverse transcriptase dimerization in a model HIV-1 polyprotein.Protein science : a publication of the Protein Society · 2024Article
- Combating antimicrobial resistance in malaria, HIV and tuberculosis.Nature reviews. Drug discovery · 2024Review
- HIV-1 protease inhibitors with a P1 phosphonate modification maintain potency against drug-resistant variants by increased interactions with flap residues.European journal of medicinal chemistry · 2023Article
- Evolving Mutational Buildup in HIV-1 Protease Shifts Conformational Dynamics to Gain Drug Resistance.Journal of chemical information and modeling · 2023Article
- Article
- Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease.International journal of molecular sciences · 2022Review
- HIV-1 Integrase Inhibitors with Modifications That Affect Their Potencies against Drug Resistant Integrase Mutants.ACS infectious diseases · 2021Article
- Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.Chemical reviews · 2021Review
- Inhibiting HTLV-1 Protease: A Viable Antiviral Target.ACS chemical biology · 2021Article
- 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
- Viral proteases: Structure, mechanism and inhibition.The Enzymes · 2021Article
- Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere.Journal of medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.
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Registered trials
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.