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

Lazaros Melidis, Harriet J. Hill, Nicholas J. Coltman, Scott P. Davies, Kinga Winczura, Tasha Chauhan, James S. Craig, Aditya Garai, Catherine A.J. Hooper, Ross T. Egan, Jane A. McKeating, Nikolas J. Hodges, Zania Stamataki, Pawel Grzechnik, Michael J. Hannon

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)18144-18151
Number of pages8
JournalAngewandte Chemie - International Edition
Volume60
Issue number33
DOIs
Publication statusPublished - 9 Aug 2021

Keywords

  • inhibitors
  • metals in medicine
  • RNA structures
  • SARS-CoV-2
  • supramolecular chemistry

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