Pharmacophore-Based Discovery of Viral RNA Conformational Modulators
New RNA-binding small-molecule scaffolds are needed to unleash the pharmacological potential of RNA targets. Here we have applied a pharmacophore-based virtual screening approach, seldom used in the RNA recognition field, to identify novel conformational inhibitors of the hepatitis C virus internal...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad Católica de Valencia San Vicente Mártir |
| Repositorio: | RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir |
| Idioma: | inglés |
| OAI Identifier: | oai:riucv.ucv.es:20.500.12466/7180 |
| Acceso en línea: | https://hdl.handle.net/20.500.12466/7180 |
| Access Level: | acceso abierto |
| Palabra clave: | Bulge Drug Hepatitis C virus IRES Junction Pharmacophore RNA 32 Ciencias Médicas |
| Sumario: | New RNA-binding small-molecule scaffolds are needed to unleash the pharmacological potential of RNA targets. Here we have applied a pharmacophore-based virtual screening approach, seldom used in the RNA recognition field, to identify novel conformational inhibitors of the hepatitis C virus internal ribosome entry site. The conformational effect of the screening hits was assessed with a fluorescence resonance energy transfer assay, and the affinity, specificity, and binding site of the ligands were determined using a combination of fluorescence intensity and NMR spectroscopy experiments. The results indicate that this strategy can be successfully applied to discover RNA conformational inhibitors bearing substantially less positive charge than the reference ligands. This methodology can potentially be accommodated to other RNA motifs of pharmacological interest, facilitating the discovery of novel RNA-targeted molecules. |
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