Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase.
| العنوان: | Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase. |
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| المؤلفون: | Shannon A; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Selisko B; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Le N; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Huchting J; University of Hamburg, Faculty of Sciences, Department of Chemistry, Organic Chemistry, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany., Touret F; Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France., Piorkowski G; Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France., Fattorini V; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Ferron F; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Decroly E; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France., Meier C; University of Hamburg, Faculty of Sciences, Department of Chemistry, Organic Chemistry, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany., Coutard B; Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France., Peersen O; Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA., Canard B; Architecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, Polytech Case 925, 13009 Marseille, France. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2020 May 15. Date of Electronic Publication: 2020 May 15. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19. Competing Interests: Competing interests: Authors declare no competing interests. |
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| معلومات مُعتمدة: | R01 AI059130 United States AI NIAID NIH HHS; R37 AI059130 United States AI NIAID NIH HHS; R56 AI059130 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20200609 Latest Revision: 20240330 |
| رمز التحديث: | 20240330 |
| مُعرف محوري في PubMed: | PMC7263509 |
| DOI: | 10.1101/2020.05.15.098731 |
| PMID: | 32511380 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2020.05.15.098731 |
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