ArticleProceedings of the National Academy of Sciences of the United States of America2017
Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. 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.
- Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design.Acta pharmaceutica Sinica. B · 2026Review
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Covalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase.European journal of medicinal chemistry · 2023Article
- Modern Alchemical Free Energy Methods for Drug Discovery Explained.ACS physical chemistry Au · 2023Review
- Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).Viruses · 2023Review
- Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase.Bioorganic & medicinal chemistry letters · 2023Article
- Covalently Targeted Highly Conserved Tyr318 to Improve the Drug Resistance Profiles of HIV-1 NNRTIs: A Proof-of-Concept Study.International journal of molecular sciences · 2023Article
- Advanced approaches of developing targeted covalent drugs.RSC medicinal chemistry · 2022Review
- Covalent Modification of the JH2 Domain of Janus Kinase 2.ACS medicinal chemistry letters · 2022Article
- Newly Emerging Strategies in Antiviral Drug Discovery: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Anniversary.Molecules (Basel, Switzerland) · 2022Review
- Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.Frontiers in molecular biosciences · 2022Article
- The Fellowship of Privileged Scaffolds-One Structure to Inhibit Them All.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.Chemical reviews · 2021Review
- Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead.ACS medicinal chemistry letters · 2021Article
- Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site.Protein science : a publication of the Protein Society · 2020Article
- Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.Current opinion in structural biology · 2020Review
- Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root.European journal of medicinal chemistry · 2020Article
- LigBuilder V3: A Multi-TargetFrontiers in chemistry · 2020Article
- Structural insights into the recognition of nucleoside reverse transcriptase inhibitors by HIV-1 reverse transcriptase: First crystal structures with reverse transcriptase and the active triphosphate forms of lamivudine and emtricitabine.Protein science : a publication of the Protein Society · 2019Article
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9 authors.
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Abstract
Development of resistance remains a major challenge for drugs to treat HIV-1 infections, including those targeting the essential viral polymerase, HIV-1 reverse transcriptase (RT). Resistance associated with the Tyr181Cys mutation in HIV-1 RT has been a key roadblock in the discovery of nonnucleoside RT inhibitors (NNRTIs). It is the principal point mutation that arises from treatment of HIV-infected patients with nevirapine, the first-in-class drug still widely used, especially in developing countries. We report covalent inhibitors of Tyr181Cys RT (CRTIs) that can completely knock out activity of the resistant mutant and of the particularly challenging Lys103Asn/Tyr181Cys variant. Conclusive evidence for the covalent modification of Cys181 is provided from enzyme inhibition kinetics, mass spectrometry, protein crystallography, and antiviral activity in infected human T-cell assays. The CRTIs are also shown to be selective for Cys181 and have lower cytotoxicity than the approved NNRTI drugs efavirenz and rilpivirine.
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