ArticleCell chemical biology2024
PROTAC-mediated degradation of HIV-1 Nef efficiently restores cell-surface CD4 and MHC-I expression and blocks HIV-1 replication.
Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Global research trends and hotspots in human immunodeficiency virus-associated cervical cancer (1990-2025): a multi-database bibliometric analysis.Frontiers in immunology · 2026Pooled it
- Targeted degradation of Influenza a virus nucleoprotein via aptamer-based PROTACs for antiviral therapy.Virulence · 2026Article
- Performance of Rilpivirine-Based Hydrophobic Tags and PROTACs Directed Against HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Targeted Degradation of Picornaviral 3C Protease via PROTACs Confers High Barrier to Viral Resistance and Broad-Spectrum Antiviral Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rational Design of Broad-Spectrum Anti-Enteroviral Molecular Glues Targeting Enteroviral RNAi Suppressors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanobody-based bioPROTAC for viral protein degradation provides an antiviral strategy for porcine arterivirus.Journal of nanobiotechnology · 2026Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors.Nature communications · 2026Article
- The race between viral immune evasion and the MHC class I antigen processing pathway.FEMS microbiology reviews · 2026Review
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- Pathogen virulence genes: Advances, challenges and future directions in infectious disease research (Review).International journal of molecular medicine · 2025Review
- PROTACs in Antivirals: Current Advancements and Future Perspectives.Molecules (Basel, Switzerland) · 2025Review
- TrypPROTACs Unlocking New Therapeutic Strategies for Chagas Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- PROTAC Technology as a New Tool for Modern Pharmacotherapy.Molecules (Basel, Switzerland) · 2025Review
- Targeted protein degraders of SARS-CoV-2 Mpro are more active than enzymatic inhibition alone with activity against nirmatrelvir resistant virus.Communications medicine · 2025Article
- Review
- A First-in-Class Dual Degrader of Bcl-2/Bcl-xL Reverses HIV Latency and Minimizes Ex Vivo Reservoirs from Patients.International journal of molecular sciences · 2025Article
- Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.Cellular and molecular life sciences : CMLS · 2025Review
- Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV.Nature communications · 2025Article
- PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens.FEMS microbiology reviews · 2025Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
The HIV-1 Nef accessory factor enhances the viral life cycle in vivo, promotes immune escape of HIV-infected cells, and represents an attractive antiretroviral drug target. However, Nef lacks enzymatic activity and an active site, complicating traditional occupancy-based drug development. Here we describe the development of proteolysis targeting chimeras (PROTACs) for the targeted degradation of Nef. Nef-binding compounds, based on an existing hydroxypyrazole core, were coupled to ligands for ubiquitin E3 ligases via flexible linkers. The resulting bivalent PROTACs induced formation of a ternary complex between Nef and the cereblon E3 ubiquitin ligase thalidomide-binding domain in vitro and triggered Nef degradation in a T cell expression system. Nef-directed PROTACs efficiently rescued Nef-mediated MHC-I and CD4 downregulation in T cells and suppressed HIV-1 replication in donor PBMCs. Targeted degradation is anticipated to reverse all HIV-1 Nef functions and may help restore adaptive immune responses against HIV-1 reservoir cells in vivo.
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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 Socratic graph.