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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-spec...

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Detalles Bibliográficos
Autores principales: Uemura, Kentaro, Nobori, Haruaki, Sato, Akihiko, Toba, Shinsuke, Kusakabe, Shinji, Sasaki, Michihito, Tabata, Koshiro, Matsuno, Keita, Maeda, Naoyoshi, Ito, Shiori, Tanaka, Mayu, Anraku, Yuki, Kita, Shunsuke, Ishii , Mayumi, Kanamitsu, Kayoko, Orba, Yasuko, Matsuura, Yoshiharu, Hall, William W., Sawa, Hirofumi, Kida, Hiroshi, Matsuda, Akira, Maenaka, Katsumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10589713/
https://www.ncbi.nlm.nih.gov/pubmed/37831739
http://dx.doi.org/10.1073/pnas.2304139120
Descripción
Sumario: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.