ArticleThe Journal of biological chemistry2015
Identification of a novel HIV-1 inhibitor targeting Vif-dependent degradation of human APOBEC3G protein.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Overview of host-directed antiviral targets for future research and drug development.Acta pharmaceutica Sinica. B · 2025Review
- Review
- A high-throughput response to the SARS-CoV-2 pandemic.SLAS discovery : advancing life sciences R & D · 2024Article
- Design of Vif-Derived Peptide Inhibitors with Anti-HIV-1 Activity by Interrupting Vif-CBFβ Interaction.Viruses · 2024Article
- Engineered deaminases as a key component of DNA and RNA editing tools.Molecular therapy. Nucleic acids · 2023Review
- Aromatic disulfides as potential inhibitors against interaction between deaminase APOBEC3G and HIV infectivity factor.Acta biochimica et biophysica Sinica · 2022Article
- Multifaceted HIV-1 Vif interactions with human E3 ubiquitin ligase and APOBEC3s.The FEBS journal · 2021Article
- The Role of APOBECs in Viral Replication.Microorganisms · 2020Review
- A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting vif/CBFβ interaction.The Journal of biological chemistry · 2020Article
- Inhibition of Vif-Mediated Degradation of APOBEC3G through Competitive Binding of Core-Binding Factor Beta.Journal of virology · 2020Article
- Article
- ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.Cell host & microbe · 2019Article
- Identification of small molecule compounds targeting the interaction of HIV-1 Vif and human APOBEC3G by virtual screening and biological evaluation.Scientific reports · 2018Article
- A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 from HIV Vif-Dependent Degradation.Trends in molecular medicine · 2018Review
- APOBEC Enzymes as Targets for Virus and Cancer Therapy.Cell chemical biology · 2018Review
- Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1.Frontiers in immunology · 2018Review
- Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.PLoS pathogens · 2018Article
- 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2'-Deoxycytidine.Antimicrobial agents and chemotherapy · 2016Article
- A Review of Functional Motifs Utilized by Viruses.Proteomes · 2016Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
APOBEC3G (A3G) is a cellular cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA and by deamination-independent mechanisms. HIV-1 Vif binds to A3G, resulting in its degradation via the 26 S proteasome. Therefore, this interaction represents a potential therapeutic target. To identify compounds that inhibit interaction between A3G and HIV-1 Vif in a high throughput format, we developed a homogeneous time-resolved fluorescence resonance energy transfer assay. A 307,520 compound library from the NIH Molecular Libraries Small Molecule Repository was screened. Secondary screens to evaluate dose-response performance and off-target effects, cell-based assays to identify compounds that attenuate Vif-dependent degradation of A3G, and assays testing antiviral activity in peripheral blood mononuclear cells and T cells were employed. One compound, N.41, showed potent antiviral activity in A3G(+) but not in A3G(-) T cells and had an IC50 as low as 8.4 μM and a TC50 of >100 μM when tested against HIV-1Ba-L replication in peripheral blood mononuclear cells. N.41 inhibited the Vif-A3G interaction and increased cellular A3G levels and incorporation of A3G into virions, thereby attenuating virus infectivity in a Vif-dependent manner. N.41 activity was also species- and Vif-dependent. Preliminary structure-activity relationship studies suggest that a hydroxyl moiety located at a phenylamino group is critical for N.41 anti-HIV activity and identified N.41 analogs with better potency (IC50 as low as 4.2 μM). These findings identify a new lead compound that attenuates HIV replication by liberating A3G from Vif regulation and increasing its innate antiviral activity.
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