Here, we describe the discovery of compounds that inhibit self-splicing in group II introns. Using docking calculations, we targeted the catalytic active site within the Oceanobacillus iheyensis group IIC intron and virtually screened a library of lead-like compounds. From this initial virtual screen, we identified three unique scaffolds that inhibit splicing in vitro. Additional tests revealed that an analog of the lead scaffold inhibits splicing in an intron-dependent manner. Furthermore, this analog exhibited activity against the group II intron from a different class: the yeast ai5γ IIB intron. The splicing inhibitors we identified could serve as chemical tools for developing group II intron-targeted antifungals, and, more broadly, our results highlight the potential of in silico techniques for identifying bioactive hits against structured and functionally complex RNAs.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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