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

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Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*. / Melidis, Lazaros; Hill, Harriet J; Coltman, Nicholas J; Davies, Scott P; Winczura, Kinga; Chauhan, Tasha; Craig, James S; Garai, Aditya; Hooper, Catherine A J; Egan, Ross T; McKeating, Jane A; Hodges, Nikolas J; Stamataki, Zania; Grzechnik, Pawel; Hannon, Michael J.

In: Angewandte Chemie (International Edition) , 29.04.2021.

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@article{25ddede5188a43b5b27a05d3dccafa8f,
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.",
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}",
note = "{\textcopyright} 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",
year = "2021",
month = apr,
day = "29",
doi = "10.1002/anie.202104179",
language = "English",
journal = "Angewandte Chemie (International Edition) ",
issn = "1433-7851",
publisher = "Wiley-VCH Verlag",

}

RIS

TY - JOUR

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

N1 - © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

PY - 2021/4/29

Y1 - 2021/4/29

N2 - 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.

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.

U2 - 10.1002/anie.202104179

DO - 10.1002/anie.202104179

M3 - Article

C2 - 33915014

JO - Angewandte Chemie (International Edition)

JF - Angewandte Chemie (International Edition)

SN - 1433-7851

ER -