ArticleNature communications2025
Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5' untranslated region.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research.Microbial biotechnology · 2026Review
- Site-Selective Ligand Selection by Mutational Profiling for Covalent RNA Targeting.Angewandte Chemie (International ed. in English) · 2026Article
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- SHAPE-Based Chemical Probes for Studying preQACS chemical biology · 2025Article
- Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras.bioRxiv : the preprint server for biology · 2025Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Mechanistic studies of small molecule ligands selective to RNA single G bulges.Nucleic acids research · 2025Article
- Article
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- Heterobifunctional small molecules to modulate RNA function.Trends in pharmacological sciences · 2024Review
- 2'-OH as a universal handle for studying intracellular RNAs.Cell chemical biology · 2024Review
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6 authors.
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Abstract
One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) which are often essential for viral replication, transcription, or translation. In this report, we discovered a series of coumarin derivatives that bind to a four-way RNA helix called SL5 in the 5' UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a sequencing-based method namely cgSHAPE-seq, in which an acylating probe was directed to crosslink with the 2'-OH group of ribose at the binding site to create read-through mutations during reverse transcription. cgSHAPE-seq unambiguously determined a bulged G in SL5 as the primary binding site, which was validated through mutagenesis and in vitro binding experiments. The coumarin derivatives were further used as a warhead in designing RNA-degrading chimeras to reduce viral RNA expression levels. The optimized RNA-degrading chimera C64 inhibited live virus replication in lung epithelial carcinoma cells.
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