ArticleRetrovirology2011
The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles.
Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Synthesis ofMagnetic resonance in chemistry : MRC · 2026Article
- Inhibitors of HIV-1 maturation modulate conformational dynamics and heterogeneity of the immature Gag lattice.bioRxiv : the preprint server for biology · 2026Article
- Review
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- Article
- Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.Science advances · 2022Article
- Review
- Derivation and characterization of an HIV-1 mutant that rescues IPRetrovirology · 2021Article
- CryoET structures of immature HIV Gag reveal six-helix bundle.Communications biology · 2021Article
- HIV-1 Maturation: Lessons Learned from Inhibitors.Viruses · 2020Review
- Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs.Molecules (Basel, Switzerland) · 2019Review
- Maturation of retroviruses.Current opinion in virology · 2019Review
- Resistance to Second-Generation HIV-1 Maturation Inhibitors.Journal of virology · 2019Article
- Second Generation Inhibitors of HIV-1 Maturation.ACS medicinal chemistry letters · 2019Article
- MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy.Molecules (Basel, Switzerland) · 2018Review
- Quenching protein dynamics interferes with HIV capsid maturation.Nature communications · 2017Article
- The Second-Generation Maturation Inhibitor GSK3532795 Maintains Potent Activity Toward HIV Protease Inhibitor-Resistant Clinical Isolates.Journal of acquired immune deficiency syndromes (1999) · 2017Article
- Structural biology of supramolecular assemblies by magic-angle spinning NMR spectroscopy.Quarterly reviews of biophysics · 2017Review
- Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors.PLoS pathogens · 2016Article
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7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundBevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1) maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1 infected patients. In contrast to inhibitors that target the active site of the viral protease, bevirimat specifically inhibits a single cleavage event, the final processing step for the Gag precursor where p25 (CA-SP1) is cleaved to p24 (CA) and SP1.
resultsIn this study, photoaffinity analogs of bevirimat and mass spectrometry were employed to map the binding site of bevirimat to Gag within immature virus-like particles. Bevirimat analogs were found to crosslink to sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with previous biochemical data on the effect of bevirimat on Gag processing and with genetic data from resistance mutations, in a region predicted by NMR and mutational studies to have α-helical character. Unexpectedly, a second region of interaction was found within the Major Homology Region (MHR). Extensive prior genetic evidence suggests that the MHR is critical for virus assembly.
conclusionsThis is the first demonstration of a direct interaction between the maturation inhibitor, bevirimat, and its target, Gag. Information gained from this study sheds light on the mechanisms by which the virus develops resistance to this class of drug and may aid in the design of next-generation maturation inhibitors.
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