ArticleAntimicrobial agents and chemotherapy2013
Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances.PLoS pathogens · 2026Review
- 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
- TARDBP as a regulator of HIV-1 assembly and infection: a review of targeting the viral capsid precursor Pr55Gag and limiting viral core entry.Cell communication and signaling : CCS · 2026Review
- Preclinical virology profiles of the HIV-1 capsid inhibitors VH4004280 and VH4011499.Antimicrobial agents and chemotherapy · 2025Article
- Structural basis for HIV-1 capsid adaption to a deficiency in IP6 packaging.Nature communications · 2025Article
- Understanding the HIV-CA protein and the ligands that bind at the N-terminal domain (NTD) - C-terminal domain (CTD) interface.RSC medicinal chemistry · 2025Review
- The identification of a novel interaction site for the human immunodeficiency virus capsid on nucleoporin 153.The Journal of general virology · 2025Article
- Kinetic implications of IPScience advances · 2025Article
- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- Review
- The capsid revolution.Journal of molecular cell biology · 2024Review
- Article
- Biochemical Detection of Capsid in the Nucleus During HIV-1 Infection.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.Journal of virology · 2023Review
- Use of TSAR, Thermal Shift Analysis in R, to identify Folic Acid as a Molecule that Interacts with HIV-1 Capsid.bioRxiv : the preprint server for biology · 2023Article
- Synthesis and clinical application of new drugs approved by FDA in 2022.Molecular biomedicine · 2023Review
- The HIV-1 capsid core is an opportunistic nuclear import receptor.Nature communications · 2023Article
- A Broad-Spectrum Antiviral Molecule, Protoporphyrin IX, Acts as a Moderator of HIV-1 Capsid Assembly by Targeting the Capsid Hexamer.Microbiology spectrum · 2023Article
- Low-molecular-weight anti-HIV-1 agents targeting HIV-1 capsid proteins.RSC advances · 2023Article
- Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors ofFrontiers in tropical diseases · 2023Article
28 more citing papers are in PubMed but not listed here.
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13 authors.
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Abstract
The identification of novel antiretroviral agents is required to provide alternative treatment options for HIV-1-infected patients. The screening of a phenotypic cell-based viral replication assay led to the identification of a novel class of 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6-one (pyrrolopyrazolone) HIV-1 inhibitors, exemplified by two compounds: BI-1 and BI-2. These compounds inhibited early postentry stages of viral replication at a step(s) following reverse transcription but prior to 2 long terminal repeat (2-LTR) circle formation, suggesting that they may block nuclear targeting of the preintegration complex. Selection of viruses resistant to BI-2 revealed that substitutions at residues A105 and T107 within the capsid (CA) amino-terminal domain (CANTD) conferred high-level resistance to both compounds, implicating CA as the antiviral target. Direct binding of BI-1 and/or BI-2 to CANTD was demonstrated using isothermal titration calorimetry and nuclear magnetic resonance (NMR) chemical shift titration analyses. A high-resolution crystal structure of the BI-1:CANTD complex revealed that the inhibitor bound within a recently identified inhibitor binding pocket (CANTD site 2) between CA helices 4, 5, and 7, on the surface of the CANTD, that also corresponds to the binding site for the host factor CPSF-6. The functional consequences of BI-1 and BI-2 binding differ from previously characterized inhibitors that bind the same site since the BI compounds did not inhibit reverse transcription but stabilized preassembled CA complexes. Hence, this new class of antiviral compounds binds CA and may inhibit viral replication by stabilizing the viral capsid.
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