Small-Molecule Antiviral β- <scp>d</scp> - <i>N</i> <sup>4</sup> -Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance
-
- Maria L. Agostini
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Andrea J. Pruijssers
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- James D. Chappell
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Jennifer Gribble
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Xiaotao Lu
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Erica L. Andres
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Gregory R. Bluemling
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- Mark A. Lockwood
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- Timothy P. Sheahan
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
-
- Amy C. Sims
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
-
- Michael G. Natchus
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- Manohar Saindane
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- Alexander A. Kolykhalov
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- George R. Painter
- Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA
-
- Ralph S. Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
-
- Mark R. Denison
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
-
- Tom Gallagher
- editor
書誌事項
- 公開日
- 2019-12
- 権利情報
-
- https://journals.asm.org/non-commercial-tdm-license
- DOI
-
- 10.1128/jvi.01348-19
- 公開者
- American Society for Microbiology
この論文をさがす
説明
<jats:p> The emergence of coronaviruses (CoVs) into human populations from animal reservoirs has demonstrated their epidemic capability, pandemic potential, and ability to cause severe disease. However, no antivirals have been approved to treat these infections. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, β- <jats:sc>d</jats:sc> - <jats:italic>N</jats:italic> <jats:sup>4</jats:sup> -hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. Further, passage in the presence of NHC generates only low-level resistance, likely due to the accumulation of multiple potentially deleterious transition mutations. Together, these data support a mutagenic mechanism of inhibition by NHC and further support the development of NHC for treatment of CoV infections. </jats:p>
収録刊行物
-
- Journal of Virology
-
Journal of Virology 93 (24), e01348-19-, 2019-12
American Society for Microbiology
