ArticleScience (New York, N.Y.)2020
Structural basis of second-generation HIV integrase inhibitor action and viral resistance.
Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 104 citations in OpenAlex.
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Core nucleosomes are refractory to lentiviral DNA integration.Nature communications · 2026Article
- Predicting water at the protein interface in cryo-EM structures from MD-excess chemical potential.Biophysical journal · 2026Article
- Molecular basis for the regulation of retroviral nucleosomal integration by chromatin compaction.Nucleic acids research · 2026Article
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Review
- Dolutegravir developmental toxicity is mitigated by magnesium and folate in zebrafish embryos.Disease models & mechanisms · 2026Article
- Article
- Delineation of a novel assembly intermediate in Rous sarcoma virus integration pathway.Nucleic acids research · 2026Article
- Retroviral intasome architecture shapes the dynamics of target DNA search and integration.PLoS pathogens · 2026Article
- Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.Nature communications · 2025Article
- Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors.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
- Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Article
- Article
- GOLEM: Automated and Robust Cryo-EM-Guided Ligand Docking with Explicit Water Molecules.Journal of chemical information and modeling · 2024Article
- Article
- Article
- HIV-1 Integrase Assembles Multiple Species of Stable Synaptic Complex Intasomes That Are Active for Concerted DNA Integration In vitro.Journal of molecular biology · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Although second-generation HIV integrase strand-transfer inhibitors (INSTIs) are prescribed throughout the world, the mechanistic basis for the superiority of these drugs is poorly understood. We used single-particle cryo-electron microscopy to visualize the mode of action of the advanced INSTIs dolutegravir and bictegravir at near-atomic resolution. Glutamine-148→histidine (Q148H) and glycine-140→serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations. Our results reveal that binding to magnesium ions underpins a fundamental weakness of the INSTI pharmacophore that is exploited by the virus to engender resistance and provide a structural framework for the development of this class of anti-HIV/AIDS therapeutics.
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What OpenQuestion holds
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.