Restriction of SARS-CoV-2 Replication by Targeting Programmed −1 Ribosomal Frameshifting In Vitro
SUMMARY Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires programmed −1 ribosomal frameshifting (−1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in −1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a −1 PRF inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on −1 PRF of other beta coronaviruses. Importantly, frameshift inhibition by merafloxacin substantially impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing the proof of principle of targeting −1 PRF as an effective antiviral strategy for SARS-CoV-2..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 24. Nov. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Yu [VerfasserIn] |
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| doi: |
10.1101/2020.10.21.349225 |
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| PPN (Katalog-ID): |
XBI019167059 |
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| 245 | 1 | 0 | |a Restriction of SARS-CoV-2 Replication by Targeting Programmed −1 Ribosomal Frameshifting In Vitro |
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| 520 | |a SUMMARY Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires programmed −1 ribosomal frameshifting (−1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in −1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a −1 PRF inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on −1 PRF of other beta coronaviruses. Importantly, frameshift inhibition by merafloxacin substantially impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing the proof of principle of targeting −1 PRF as an effective antiviral strategy for SARS-CoV-2. | ||
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| 700 | 1 | |a Abriola, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Surovtseva, Yulia V. |e verfasserin |4 aut | |
| 700 | 1 | |a Lindenbach, Brett D. |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Junjie U. |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.10.21.349225 |z kostenfrei |3 Volltext |
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