ArticleScience advances2023
Mechanisms of HIV-1 integrase resistance to dolutegravir and potent inhibition of drug-resistant variants.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 33 citations in OpenAlex.
- Predicting water at the protein interface in cryo-EM structures from MD-excess chemical potential.Biophysical journal · 2026Article
- MBind: A Web-Based Platform for Metalloprotein and Nonmetalloprotein Docking with Optional ML Docking Integration.Molecules (Basel, Switzerland) · 2026Article
- Pretreatment Resistance to Integrase Inhibitors in the Swiss HIV Cohort Study From 1995 to 2025.Open forum infectious diseases · 2026Article
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Machine Learning Identifies Potential Accessory Resistance-Associated Mutations in HIV-1 Integrase.Research square · 2026Article
- Mutation-Tolerant Inhibition of HIV-1 Integrase Strand Transfer by Secondary Metabolites from the Endophytic FungusMicroorganisms · 2026Article
- Review
- Safety and efficacy of albuvirtide and dolutegravir for HIV postexposure prophylaxis in men who have sex with men: a prospective non-randomized cohort study.BMC infectious diseases · 2026Article
- Toward Reconciling the Standard Binding Free Energy of Lenacapavir to HIV-1 Capsid with Experiment: Thermodynamic Effects of Solvent Buffer and Ligand Reorganization.The journal of physical chemistry. B · 2026Article
- Two cases of possible transmitted HIV drug resistance to all currently available integrase inhibitors, the Netherlands, 2025.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2026Article
- DRESIS 2.0: the comprehensive landscape of drug resistance information.Nucleic acids research · 2026Article
- Predicting side chain conformations in folded proteins by AlphaFold: Perspective and challenges.Biophysical journal · 2025Article
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
- Pi-pi stacking interactions with viral DNA contribute to the potency of naphthyridine-based HIV-1 integrase inhibitors.NAR molecular medicine · 2025Article
- Clicking viruses-with chemistry toward mechanisms in infection.Journal of virology · 2025Review
- A High-Performance Liquid Chromatography-Mass Spectrometry method for simultaneous determination of dolutegravir, nevirapine, efavirenz, rifampicin and rifapentine concentrations in human plasma.medRxiv : the preprint server for health sciences · 2025Article
- Development of enhanced HIV-1 non-nucleoside reverse transcriptase inhibitors with improved resistance and pharmacokinetic profiles.Science advances · 2025Article
- De Novo Hydration of Cryo-EM Reconstructions through Molecular Dynamics Simulations of the Excess Chemical Potential.bioRxiv : the preprint server for biology · 2025Article
- Analysis of raltegravir analogs to enhance inhibitory efficiency against HIV integrase.Scientific reports · 2025Article
- Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
Abstract
HIV-1 infection depends on the integration of viral DNA into host chromatin. Integration is mediated by the viral enzyme integrase and is blocked by integrase strand transfer inhibitors (INSTIs), first-line antiretroviral therapeutics widely used in the clinic. Resistance to even the best INSTIs is a problem, and the mechanisms of resistance are poorly understood. Here, we analyze combinations of the mutations E138K, G140A/S, and Q148H/K/R, which confer resistance to INSTIs. The investigational drug 4d more effectively inhibited the mutants compared with the approved drug Dolutegravir (DTG). We present 11 new cryo-EM structures of drug-resistant HIV-1 intasomes bound to DTG or 4d, with better than 3-Å resolution. These structures, complemented with free energy simulations, virology, and enzymology, explain the mechanisms of DTG resistance involving E138K + G140A/S + Q148H/K/R and show why 4d maintains potency better than DTG. These data establish a foundation for further development of INSTIs that potently inhibit resistant forms in integrase.
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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.