Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*

Research output: Contribution to journalArticlepeer-review

Authors

External organisations

  • University of Oxford

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.

Bibliographic note

© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Details

Original languageEnglish
JournalAngewandte Chemie (International Edition)
Early online date29 Apr 2021
Publication statusE-pub ahead of print - 29 Apr 2021