A Massively Parallel Selection of Small Molecule-RNA Motif Binding Partners Informs Design of an Antiviral from Sequence
| Autor: | Jessica L. Childs-Disney, Timothy L. Tellinghuisen, Balayeshwanth R. Vummidi, Mark R. Southern, Zi-Fu Wang, Avik Biswas, Gogce Crynen, Matthew D. Disney, Sai Pradeep Velagapudi, Hafeez S. Haniff, Yasumasa Matsumoto, Tuan Tran |
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| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Chem. 4(10) |
| ISSN: | 2451-9294 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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