ArticleProceedings of the National Academy of Sciences of the United States of America2003
PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
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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
210 citing papers in PubMed.
- A phase I, first-in-human study investigating the safety, tolerability, and pharmacokinetics of the maturation inhibitor GSK3739937.Pharmacology research & perspectives · 2023Trial
- Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Antiviral Activity, Safety, and Exposure-Response Relationships of GSK3532795, a Second-Generation Human Immunodeficiency Virus Type 1 Maturation Inhibitor, Administered as Monotherapy or in Combination With Atazanavir With or Without Ritonavir in a Phase 2a Randomized, Dose-Ranging, Controlled Trial (AI468002).Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Trial
- Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.PLoS pathogens · 2012Trial
- Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection.Antimicrobial agents and chemotherapy · 2007Trial
- Safety and pharmacokinetics of Bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers.Antimicrobial agents and chemotherapy · 2007Trial
- Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers.Clinical pharmacokinetics · 2007Trial
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Synthesis ofMagnetic resonance in chemistry : MRC · 2026Article
- Lenacapavir binding to immature Gag induces giant virions and causes protease-dependent inhibition of viral release.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cryo-ET reveals distinct Gag lattice architectures in virus-like particles and immature HIV-1.Structure (London, England : 1993) · 2026Article
- Distinct Target Site of Lenacapavir in Immature HIV-1 and Concurrent Binding with the Maturation Inhibitor Bevirimat.Journal of the American Chemical Society · 2025Article
- Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.Molecules (Basel, Switzerland) · 2025Review
- Structural Basis for HIV-1 Maturation Inhibition by PF-46396 Determined by MAS NMR.Journal of the American Chemical Society · 2025Article
- How Can Plant-Derived Natural Products and Plant Biotechnology Help Against Emerging Viruses?International journal of molecular sciences · 2025Review
- Betulinic Acid ω-Triphenylphosphonium Alkyl Esters: Antiproliferative Activities and In Silico Pharmacokinetic Profiles.Biomedicines · 2025Article
- Structural insights into inhibitor mechanisms on immature HIV-1 Gag lattice revealed by high-resolutionbioRxiv : the preprint server for biology · 2024Article
- Article
- Review
- Function-Oriented Synthesis of Pentacyclic Triterpenoids and Discovery of anOrganic letters · 2024Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
New HIV therapies are urgently needed to address the growing problem of drug resistance. In this article, we characterize the anti-HIV drug candidate 3-O-(3',3'-dimethylsuccinyl) betulinic acid (PA-457). We show that PA-457 potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). We find that virions from PA-457-treated cultures are noninfectious and exhibit an aberrant particle morphology characterized by a spherical, acentric core and a crescent-shaped, electron-dense shell lying just inside the viral membrane. To identify the determinants of compound activity we selected for PA-457-resistant virus in vitro. Consistent with the effect on Gag processing, we found that mutations conferring resistance to PA-457 map to the p25 to p24 cleavage site. PA-457 represents a unique class of anti-HIV compounds termed maturation inhibitors that exploit a previously unidentified viral target, providing additional opportunities for HIV drug discovery.
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