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Novel Inhibitors of SARS-CoV-2 RNA Identified through Virtual Screening
G. Mathez, A. Brancale, V. Cagno
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
PubMed
39037082
DOI
10.1021/acs.jcim.4c00758
Knihovny.cz E-zdroje
- MeSH
- antivirové látky * farmakologie chemie MeSH
- konformace nukleové kyseliny MeSH
- lidé MeSH
- molekulární modely MeSH
- preklinické hodnocení léčiv * metody MeSH
- RNA virová * metabolismus antagonisté a inhibitory genetika MeSH
- SARS-CoV-2 * účinky léků MeSH
- simulace molekulového dockingu MeSH
- uživatelské rozhraní počítače MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
We currently lack antivirals for most human viruses. In a quest for new molecules, focusing on viral RNA, instead of viral proteins, can represent a promising strategy. In this study, new inhibitors were identified starting from a published crystal structure of the tertiary SARS-CoV-2 RNA involved in the -1 programmed ribosomal frameshift. The pseudoknot structure was refined, and a virtual screening was performed using the repository of binders to the nucleic acid library, taking into consideration RNA flexibility. Hit compounds were validated against the wild-type virus and with a dual-luciferase assay measuring the frameshift efficiency. Several active molecules were identified. Our study reveals new inhibitors of SARS-CoV-2 but also highlights the feasibility of targeting RNA starting from virtual screening, a strategy that could be broadly applied to drug development.
Citace poskytuje Crossref.org
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