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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/6/748 |
| _version_ | 1827657648538910720 |
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| author | María Martín-Villamil Isaías Sanmartín Ángela Moreno José Gallego |
| author_facet | María Martín-Villamil Isaías Sanmartín Ángela Moreno José Gallego |
| author_sort | María Martín-Villamil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T22:47:00Z |
| format | Article |
| id | doaj.art-faa1484058a045a49be30bf7d7f34da6 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:00Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-faa1484058a045a49be30bf7d7f34da62023-11-23T18:28:03ZengMDPI AGPharmaceuticals1424-82472022-06-0115674810.3390/ph15060748Pharmacophore-Based Discovery of Viral RNA Conformational ModulatorsMaría Martín-Villamil0Isaías Sanmartín1Ángela Moreno2José Gallego3Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2, 46001 Valencia, SpainCentro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2, 46001 Valencia, SpainCentro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2, 46001 Valencia, SpainCentro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, C/Quevedo 2, 46001 Valencia, SpainNew 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.https://www.mdpi.com/1424-8247/15/6/748bulgedrughepatitis C virusIRESjunctionpharmacophore |
| spellingShingle | María Martín-Villamil Isaías Sanmartín Ángela Moreno José Gallego Pharmacophore-Based Discovery of Viral RNA Conformational Modulators Pharmaceuticals bulge drug hepatitis C virus IRES junction pharmacophore |
| title | Pharmacophore-Based Discovery of Viral RNA Conformational Modulators |
| title_full | Pharmacophore-Based Discovery of Viral RNA Conformational Modulators |
| title_fullStr | Pharmacophore-Based Discovery of Viral RNA Conformational Modulators |
| title_full_unstemmed | Pharmacophore-Based Discovery of Viral RNA Conformational Modulators |
| title_short | Pharmacophore-Based Discovery of Viral RNA Conformational Modulators |
| title_sort | pharmacophore based discovery of viral rna conformational modulators |
| topic | bulge drug hepatitis C virus IRES junction pharmacophore |
| url | https://www.mdpi.com/1424-8247/15/6/748 |
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