Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.

ABSTRACT: Targeting RNA including viral RNAs with small molecules is an emerging field. The hepatitis C virus internal ribosome entry site (HCV IRES) is a potential target for translation inhibitor development to raise drug resistance mutation preparedness. Using RNA-focused and unbiased molecule libraries, a structure-based virtual screening (VS) by molecular docking and pharmacophore analysis was performed against the HCV IRES subdomain IIa. VS hits were validated by a microscale thermophoresis (MST) binding assay and a Förster resonance energy transfer (FRET) assay elucidating ligand-induced conformational changes. Ten hit molecules were identified with potencies in the high to medium micromolar range proving the suitability of structure-based virtual screenings against RNA-targets. Hit compounds

SUBMITTER: Kallert E 

PROVIDER: S-EPMC11110755 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature