RNA-targeted aminopyridine compounds provide a new antifungal strategy

Lead aminopyridine 56 binds the Candida albicans mtLSU group I intron and inhibits splicing with an IC 21.6 nM potency.

• Why it matters: RNA-targeted therapeutics are constrained by the lack of well-defined RNA targets where ligand binding can be linked to measurable function, and by the need for selective antifungal mechanisms.
• What they did: The team recalibrated an intron-splicing assay toward cellular conditions and ran a cryo-EM-guided structure–activity relationship campaign against the Candida albicans mtLSU intron.
• The result: Flexible diamine-containing ligands outperformed constrained analogues, and compound 56 synergized with amphotericin B while RT-qPCR confirmed direct target engagement in cells.

AI summary of the abstract · may contain errors · not medical advice · read the paper.