Volume-1 ,Issue 3, October-2025

RNA, which includes coding mRNAs, non-coding RNAs, and structural viral elements that control gene expression, translation, and cellular homeostasis, has become a key and adaptable therapeutic target. Ribosome-directed antibiotics were once the prime example of RNA-targeting small molecules, but developments in structural biology, chemical biology, and computational modeling have broadened the RNA druggable space to include viral RNA motifs, oncogenic non-coding RNAs, and epitranscriptomic modifications. To enable rational ligand design, contemporary approaches make use of RNA chemical probing, high-throughput and fragment-based screening, NMR/cryo-EM structural insights, and AI-driven predictive modeling. New approaches to long-standing problems with selectivity, conformational heterogeneity, and cellular transport include RIBOTAC-mediated RNA degradation, covalent or reversible covalent RNA binders, and combination therapy with RNA biologics. In order to provide a foundation for creating next-generation RNA-targeted treatments, this study discusses RNA structures, small-molecule design principles, discovery methodologies, case studies, obstacles, and upcoming approaches.

Keyword: RNA–ligand interactions, structural biology, computational drug discovery, machine learning, bioactive small molecule.