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        • Universidad Jorge Tadeo Lozano (Colombia)
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        • Universidad Jorge Tadeo Lozano (Colombia)
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        Sofosbuvir terminated RNA is more resistant to SARS‐CoV‐2 proofreader than RNA terminated by Remdesivir

        Registro en:
        2045-2322
        https://doi.org/10.1038/s41598-020-73641-9
        http://hdl.handle.net/20.500.12010/14382
        https://doi.org/10.1038/s41598-020-73641-9
        http://repositorioslatinoamericanos.uchile.cl/handle/2250/3496185
        Autor
        Jockusch, Stefen
        Tao, Chuanjuan
        Li, Xiaoxu
        Chien, Minchen
        Kumar, Shiv
        Morozova, Irina
        Kalachikov, Sergey
        Russo, James J.
        Ju, Jingyue
        Institución
        • Universidad Jorge Tadeo Lozano (Colombia)
        Resumen
        SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2.We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fdelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fdelity DNA polymerase. Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity.Any efective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity.We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic.These results ofer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.
        Materias
        Sofosbuvir terminated RNA
        RNA
        RNA terminated
        SARS‑CoV‑2

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        Red de Repositorios Latinoamericanos
        + de 8.000.000 publicaciones disponibles
        500 instituciones participantes
        Dirección de Servicios de Información y Bibliotecas (SISIB)
        Universidad de Chile
        Ingreso Administradores
        Colecciones destacadas
        • Tesis latinoamericanas
        • Tesis argentinas
        • Tesis chilenas
        • Tesis peruanas
        Nuevas incorporaciones
        • Argentina
        • Brasil
        • Colombia
        • México
        Dirección de Servicios de Información y Bibliotecas (SISIB)
        Universidad de Chile
        Red de Repositorios Latinoamericanos | 2006-2018