ArticlemBio2025
Structural and mechanistic bases for resistance of the M66I capsid variant to lenacapavir.
Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Structural basis of lenacapavir-induced HIV-1 capsid defects during virion maturation.Nature communications · 2026Article
- Mis-localized nucleoporin POM121C potently inhibits nuclear entry of HIV-1 but leads to the outgrowth of viral escape mutants.Journal of virology · 2026Article
- Review
- Capsid stabilization reprograms the nuclear fate of the HIV genome.Science advances · 2026Article
- Capsid and integrase play essential apposing roles in viral ribonucleoprotein assembly during HIV-1 core morphogenesis.iScience · 2026Article
- Commentary on PURPOSE-1 and PURPOSE-2 trials of lenacapavir: a breakthrough in HIV prevention.Annals of medicine and surgery (2012) · 2026Article
- Damaging the conical morphology of HIV-1 capsid by targeting the FG-binding pocket and disfavoring pentameric subunits needed for core closure.bioRxiv : the preprint server for biology · 2026Article
- Recurrent and novel evolutionary pathways drive in vitro HIV-1 lenacapavir resistance with diverse phenotypic consequences.Nature communications · 2026Article
- Lenacapavir prevents production of infectious HIV-1 by abrogating immature virus assembly.bioRxiv : the preprint server for biology · 2026Article
- ViMIC 2.0: an updated database of human disease-related viral mutations, integration sites, and multi-omics data.Nucleic acids research · 2026Article
- Lenacapavir at the Spatiotemporal Limit: Tissue Pharmacokinetics, Pharmacokinetic Tail Dynamics, and the Emergence of Capsid Resistance in Long-Acting HIV Prevention.Clinical pharmacology : advances and applications · 2026Review
- Lenacapavir-induced capsid damage uncovers HIV-1 genomes emanating from nuclear speckles.The EMBO journal · 2026Article
- Design, synthesis and profiling of highly potent antivirals targeting emerging drug-resistant HIV-1 variants.bioRxiv : the preprint server for biology · 2025Article
- Use of the Split Luciferase Complementation Assay to Identify Novel Small Molecules That Disrupt Essential Protein-Protein Interactions of Viruses.Biomolecules · 2025Article
- Delineating Structural Functionalities of Lenacapavir Amenable to Modifications for Targeting Emerging Drug-Resistant HIV‑1 Capsid Variants.ACS medicinal chemistry letters · 2025Article
- Lenacapavir-associated drug resistance: implications for scaling up long-acting HIV pre-exposure prophylaxis.The lancet. HIV · 2025Review
- Pharmacokinetics, pharmacodynamics, efficacy and drug resistance selection of injectable long-acting lenacapavir pre-exposure prophylaxis (PrEP) against HIV.medRxiv : the preprint server for health sciences · 2025Article
- Time-Resolved Fluorescence Imaging and Correlative Cryo-Electron Tomography to Study Structural Changes of the HIV-1 Capsid.ACS nano · 2025Article
- New Advances in Anti-HIV-1 Strategies Targeting the Assembly and Stability of Capsid Protein.International journal of molecular sciences · 2025Review
- High Risk, High Reward: By Selecting Tsg101, A Protein That Sorts The Trash, As Our Personal ESCRT, Both HIV And I Were Able To Bud.Journal of molecular biology · 2025Review
Corrections and comments
- Update of
Authors and funding
19 authors.
Funding
Abstract
Lenacapavir (LEN) is the first-in-class viral capsid protein (CA) targeting antiretroviral for treating multi-drug-resistant HIV-1 infection. Clinical trials and cell culture experiments have identified resistance-associated mutations (RAMs) in the vicinity of the hydrophobic CA pocket targeted by LEN. The M66I substitution conferred by far the highest level of resistance to the inhibitor compared to other RAMs. Here we investigated structural and mechanistic bases for how the M66I change affects LEN binding to CA and viral replication. The high-resolution X-ray structure of the CA(M66I) hexamer revealed that the β-branched side chain of Ile66 induces steric hindrance specifically to LEN, thereby markedly reducing the inhibitor binding affinity. By contrast, the M66I substitution did not affect the binding of Phe-Gly (FG)-motif-containing cellular cofactors CPSF6, NUP153, or SEC24C, which engage the same hydrophobic pocket of CA. In cell culture, the M66I variant did not acquire compensatory mutations. Analysis of viral replication intermediates revealed that HIV-1
Indexed as
Identifiers
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.