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A Massively Parallel Selection of Small Molecule-RNA Motif Binding Partners Informs Design of an Antiviral from Sequence
- Source :
- Chem. 4(10)
- Publication Year :
- 2019
-
Abstract
- Summary Many RNAs cause disease; however, RNA is rarely exploited as a small-molecule drug target. Our programmatic focus is to define privileged RNA motif small-molecule interactions to enable the rational design of compounds that modulate RNA biology starting from only sequence. We completed a massive, library-versus-library screen that probed over 50 million binding events between RNA motifs and small molecules. The resulting data provide a rich encyclopedia of small-molecule RNA recognition patterns, defining chemotypes and RNA motifs that confer selective, avid binding. The resulting interaction maps were mined against the entire viral genome of hepatitis C virus (HCV). A small molecule was identified that avidly bound RNA motifs present in the HCV 3′ UTR and inhibited viral replication while having no effect on host cells. Collectively, this study represents the first whole-genome pattern recognition between small molecules and RNA folds.
- Subjects :
- 0301 basic medicine
General Chemical Engineering
Hepatitis C virus
Biochemistry (medical)
Rational design
Chemical biology
RNA
General Chemistry
Computational biology
Biology
010402 general chemistry
medicine.disease_cause
01 natural sciences
Biochemistry
Small molecule
Virus
Article
0104 chemical sciences
03 medical and health sciences
030104 developmental biology
Viral replication
Materials Chemistry
Nucleic acid
medicine
Environmental Chemistry
Subjects
Details
- ISSN :
- 24519294
- Volume :
- 4
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Chem
- Accession number :
- edsair.doi.dedup.....7ce96e47b7556d88f1b4a3c630a28219