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

doi:10.1002/anie.202104179

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	18144-18151
Number of pages	8
Journal	Angewandte Chemie (International Edition)
Volume	60
Issue number	33
Early online date	29 Apr 2021
DOIs	https://doi.org/10.1002/anie.202104179
Publication status	Published - 9 Aug 2021

Bibliographical note

Keywords

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

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.202104179Licence: Creative Commons: Attribution (CC BY)

MelidisL2021SupramolecularFinal published version, 1.85 MBLicence: Creative Commons: Attribution (CC BY)

Understanding host factors that regulate the hepatitis B viral epigenome
Parish, J. (Principal Investigator)
Medical Research Council
1/10/18 → 31/07/22
Project: Research Councils

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Melidis, L., Hill, H. J., Coltman, N. J., Davies, S. P., Winczura, K., Chauhan, T., Craig, J. S., Garai, A., Hooper, C. A. J., Egan, R. T., McKeating, J. A., Hodges, N. J., Stamataki, Z., Grzechnik, P., & Hannon, M. J. (2021). Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication**. Angewandte Chemie (International Edition) , 60(33), 18144-18151. https://doi.org/10.1002/anie.202104179

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

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.",

keywords = "RNA structures, SARS-CoV-2, inhibitors, metals in medicine, supramolecular chemistry",

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

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doi = "10.1002/anie.202104179",

language = "English",

volume = "60",

pages = "18144--18151",

journal = "Angewandte Chemie (International Edition) ",

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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 & Hannon, MJ 2021, 'Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication**', Angewandte Chemie (International Edition) , vol. 60, no. 33, pp. 18144-18151. https://doi.org/10.1002/anie.202104179

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T1 - Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication**

AU - Melidis, Lazaros

AU - Hill, Harriet J

AU - Coltman, Nicholas J

AU - Davies, Scott P

AU - Winczura, Kinga

AU - Chauhan, Tasha

AU - Craig, James S

AU - Garai, Aditya

AU - Hooper, Catherine A J

AU - Egan, Ross T

AU - McKeating, Jane A

AU - Hodges, Nikolas J

AU - Stamataki, Zania

AU - Grzechnik, Pawel

AU - Hannon, Michael J

PY - 2021/8/9

Y1 - 2021/8/9

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AB - 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.

KW - RNA structures

KW - SARS-CoV-2

KW - inhibitors

KW - metals in medicine

KW - supramolecular chemistry

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SP - 18144

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JO - Angewandte Chemie (International Edition)

JF - Angewandte Chemie (International Edition)

IS - 33

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Projects

Understanding host factors that regulate the hepatitis B viral epigenome

Cite this