ArticleJournal of the American Chemical Society2019
Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Mechanistic Insights into HIV-1 Capsid Interactions with CPSF6.bioRxiv : the preprint server for biology · 2026Article
- Collective fluctuations underlying nanobody inhibitory activity targetingbioRxiv : the preprint server for biology · 2026Article
- Mechanism of HIV-1 Capsid Rupture and Uncoating by Reverse Transcription.bioRxiv : the preprint server for biology · 2026Article
- Modeling Reveals How Direct-Acting Antivirals Redirect HBV Capsid Assembly Pathways to Noninfectious Products.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic insights into lenacapavir-induced off-pathway HIV-1 capsid assembly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2025Review
- The capsid revolution.Journal of molecular cell biology · 2024Review
- HIV-1 capsid shape, orientation, and entropic elasticity regulate translocation into the nuclear pore complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Understanding Virus Structure and Dynamics through Molecular Simulations.Journal of chemical theory and computation · 2023Review
- Critical mechanistic features of HIV-1 viral capsid assembly.Science advances · 2023Article
- Bottom-up Coarse-Graining: Principles and Perspectives.Journal of chemical theory and computation · 2022Review
- Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes.Metabolites · 2022Article
- Inositol Hexakisphosphate (IP6) Accelerates Immature HIV-1 Gag Protein Assembly toward Kinetically Trapped Morphologies.Journal of the American Chemical Society · 2022Article
- Protein assembly and crowding simulations.Current opinion in structural biology · 2022Review
- Preservation of HIV-1 Gag Helical Bundle Symmetry by Bevirimat Is Central to Maturation Inhibition.Journal of the American Chemical Society · 2021Article
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- A multiscale coarse-grained model of the SARS-CoV-2 virion.Biophysical journal · 2021Article
- A new one-site coarse-grained model for water: Bottom-up many-body projected water (BUMPer). II. Temperature transferability and structural properties at low temperature.The Journal of chemical physics · 2021Article
- The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations.Computational and structural biotechnology journal · 2021Article
- Temperature and Phase Transferable Bottom-up Coarse-Grained Models.Journal of chemical theory and computation · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The early and late stages of human immunodeficiency virus (HIV) replication are orchestrated by the capsid (CA) protein, which self-assembles into a conical protein shell during viral maturation. Small molecule drugs known as capsid inhibitors (CIs) impede the highly regulated activity of CA. Intriguingly, a few CIs, such as PF-3450074 (PF74) and GS-CA1, exhibit effects at multiple stages of the viral lifecycle at effective concentrations in the pM to nM regimes, while the majority of CIs target a single stage of the viral lifecycle and are effective at nM to μM concentrations. In this work, we use coarse-grained molecular dynamics simulations to elucidate the molecular mechanisms that enable CIs to have such curious broad-spectrum activity. Our quantitatively analyzed findings show that CIs can have a profound impact on the hierarchical self-assembly of CA by perturbing populations of small CA oligomers. The self-assembly process is accelerated by the emergence of alternative assembly pathways that favor the rapid incorporation of CA pentamers, and leads to increased structural pleomorphism in mature capsids. Two relevant phenotypes are observed: (1) eccentric capsid formation that may fail to encase the viral genome and (2) rapid disassembly of the capsid, which express at late and early stages of infection, respectively. Finally, our study emphasizes the importance of adopting a dynamical perspective on inhibitory mechanisms and provides a basis for the design of future therapeutics that are effective at low stoichiometric ratios of drug to protein.
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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.