2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral ribonucleoside analogue that exhibited antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against DENV and SARS-CoV-2 but other ssRNA+ viruses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 42 vom: 17. Okt., Seite e2304139120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Uemura, Kentaro [VerfasserIn] |
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| Links: |
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| Themen: |
2-thiouridine |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 16.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2304139120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363247041 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral ribonucleoside analogue that exhibited antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against DENV and SARS-CoV-2 but other ssRNA+ viruses | ||
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| 700 | 1 | |a Nobori, Haruaki |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Akihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Toba, Shinsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kusakabe, Shinji |e verfasserin |4 aut | |
| 700 | 1 | |a Sasaki, Michihito |e verfasserin |4 aut | |
| 700 | 1 | |a Tabata, Koshiro |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuno, Keita |e verfasserin |4 aut | |
| 700 | 1 | |a Maeda, Naoyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Ito, Shiori |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Mayu |e verfasserin |4 aut | |
| 700 | 1 | |a Anraku, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kita, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Ishii, Mayumi |e verfasserin |4 aut | |
| 700 | 1 | |a Kanamitsu, Kayoko |e verfasserin |4 aut | |
| 700 | 1 | |a Orba, Yasuko |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuura, Yoshiharu |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, William W |e verfasserin |4 aut | |
| 700 | 1 | |a Sawa, Hirofumi |e verfasserin |4 aut | |
| 700 | 1 | |a Kida, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuda, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Maenaka, Katsumi |e verfasserin |4 aut | |
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