ArticleAntimicrobial agents and chemotherapy2009
New small-molecule inhibitor class targeting human immunodeficiency virus type 1 virion maturation.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
- Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study.PloS one · 2019Trial
- Structural Basis for HIV-1 Maturation Inhibition by PF-46396 Determined by MAS NMR.Journal of the American Chemical Society · 2025Article
- A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication.International journal of molecular sciences · 2024Review
- Antiviral Agents: Structural Basis of Action and Rational Design.Sub-cellular biochemistry · 2024Review
- Two structural switches in HIV-1 capsid regulate capsid curvature and host factor binding.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Specific Interaction of DARPin with HIV-1 CAViruses · 2022Article
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- CryoET structures of immature HIV Gag reveal six-helix bundle.Communications biology · 2021Article
- A stable immature lattice packages IPScience advances · 2021Article
- HIV-1 Maturation: Lessons Learned from Inhibitors.Viruses · 2020Review
- Recent Advances in HIV-1 Gag Inhibitor Design and Development.Molecules (Basel, Switzerland) · 2020Review
- Dominant Negative MA-CA Fusion Protein Is Incorporated into HIV-1 Cores and Inhibits Nuclear Entry of Viral Preintegration Complexes.Journal of virology · 2019Article
- Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle.Virologica Sinica · 2019Review
- Resistance to Second-Generation HIV-1 Maturation Inhibitors.Journal of virology · 2019Article
- Insights into the activity of maturation inhibitor PF-46396 on HIV-1 clade C.Scientific reports · 2017Article
- Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity.Antimicrobial agents and chemotherapy · 2016Article
- Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.Journal of virology · 2016Article
- Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage.Antimicrobial agents and chemotherapy · 2016Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A new small-molecule inhibitor class that targets virion maturation was identified from a human immunodeficiency virus type 1 (HIV-1) antiviral screen. PF-46396, a representative molecule, exhibits antiviral activity against HIV-1 laboratory strains and clinical isolates in T-cell lines and peripheral blood mononuclear cells (PBMCs). PF-46396 specifically inhibits the processing of capsid (CA)/spacer peptide 1 (SP1) (p25), resulting in the accumulation of CA/SP1 (p25) precursor proteins and blocked maturation of the viral core particle. Viral variants resistant to PF-46396 contain a single amino acid substitution in HIV-1 CA sequences (CAI201V), distal to the CA/SP1 cleavage site in the primary structure, which we demonstrate is sufficient to confer significant resistance to PF-46396 and 3-O-(3',3'-dimethylsuccinyl) betulinic acid (DSB), a previously described maturation inhibitor. Conversely, a single amino substitution in SP1 (SP1A1V), which was previously associated with DSB in vitro resistance, was sufficient to confer resistance to DSB and PF-46396. Further, the CAI201V substitution restored CA/SP1 processing in HIV-1-infected cells treated with PF-46396 or DSB. Our results demonstrate that PF-46396 acts through a mechanism that is similar to DSB to inhibit the maturation of HIV-1 virions. To our knowledge, PF-46396 represents the first small-molecule HIV-1 maturation inhibitor that is distinct in chemical class from betulinic acid-derived maturation inhibitors (e.g., DSB), demonstrating that molecules of diverse chemical classes can inhibit this mechanism.
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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.