1. Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*.
- Author
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Melidis L, Hill HJ, Coltman NJ, Davies SP, Winczura K, Chauhan T, Craig JS, Garai A, Hooper CAJ, Egan RT, McKeating JA, Hodges NJ, Stamataki Z, Grzechnik P, and Hannon MJ
- Subjects
- Animals, Antiviral Agents chemistry, Antiviral Agents metabolism, Chlorocebus aethiops, Coordination Complexes chemistry, Coordination Complexes metabolism, Coordination Complexes pharmacology, Genome, Viral drug effects, Macromolecular Substances chemistry, Macromolecular Substances metabolism, Metals, Heavy chemistry, Molecular Dynamics Simulation, RNA genetics, SARS-CoV-2 chemistry, Vero Cells, 5' Untranslated Regions, Antiviral Agents pharmacology, Macromolecular Substances pharmacology, RNA metabolism, SARS-CoV-2 drug effects, Virus Replication drug effects
- Abstract
The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel anti-viral agents., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
- Published
- 2021
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