Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication
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 m...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2021
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| _version_ | 1826256913969446912 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Melidis, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:09:49Z |
| format | Journal article |
| id | oxford-uuid:029eb55a-9ac5-4b54-91d7-aa94797f7bff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:09:49Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:029eb55a-9ac5-4b54-91d7-aa94797f7bff2022-03-26T08:41:49ZSupramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replicationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:029eb55a-9ac5-4b54-91d7-aa94797f7bffEnglishSymplectic ElementsWiley2021Melidis, LHill, HJColtman, NJDavies, SPWinczura, KChauhan, TCraig, JSGarai, AHooper, CAJEgan, RTMcKeating, JAHodges, NJStamataki, ZGrzechnik, PHannon, MJThe 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. |
| spellingShingle | 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 Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title | Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title_full | Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title_fullStr | Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title_full_unstemmed | Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title_short | Supramolecular cylinders target bulge structures in the 5′ UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication |
| title_sort | 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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