{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361418519220530944.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1128/jvi.01348-19"}},{"identifier":{"@type":"URI","@value":"https://journals.asm.org/doi/pdf/10.1128/JVI.01348-19"}}],"dc:title":[{"@value":"Small-Molecule Antiviral β-\n                    <scp>d</scp>\n                    -\n                    <i>N</i>\n                    <sup>4</sup>\n                    -Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n                    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-\n                    <jats:sc>d</jats:sc>\n                    -\n                    <jats:italic>N</jats:italic>\n                    <jats:sup>4</jats:sup>\n                    -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.\n                  </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381418519220531072","@type":"Researcher","foaf:name":[{"@value":"Maria L. Agostini"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530952","@type":"Researcher","foaf:name":[{"@value":"Andrea J. Pruijssers"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530944","@type":"Researcher","foaf:name":[{"@value":"James D. Chappell"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530950","@type":"Researcher","foaf:name":[{"@value":"Jennifer Gribble"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530945","@type":"Researcher","foaf:name":[{"@value":"Xiaotao Lu"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530953","@type":"Researcher","foaf:name":[{"@value":"Erica L. Andres"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530951","@type":"Researcher","foaf:name":[{"@value":"Gregory R. Bluemling"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530956","@type":"Researcher","foaf:name":[{"@value":"Mark A. Lockwood"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220531075","@type":"Researcher","foaf:name":[{"@value":"Timothy P. Sheahan"}],"jpcoar:affiliationName":[{"@value":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530946","@type":"Researcher","foaf:name":[{"@value":"Amy C. Sims"}],"jpcoar:affiliationName":[{"@value":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530955","@type":"Researcher","foaf:name":[{"@value":"Michael G. Natchus"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530947","@type":"Researcher","foaf:name":[{"@value":"Manohar Saindane"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530949","@type":"Researcher","foaf:name":[{"@value":"Alexander A. Kolykhalov"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220531074","@type":"Researcher","foaf:name":[{"@value":"George R. Painter"}],"jpcoar:affiliationName":[{"@value":"Emory Institute for Drug Development, Emory University, Atlanta, Georgia, USA"},{"@value":"Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220531073","@type":"Researcher","foaf:name":[{"@value":"Ralph S. Baric"}],"jpcoar:affiliationName":[{"@value":"Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418519220530948","@type":"Researcher","foaf:name":[{"@value":"Mark R. Denison"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"},{"@value":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1381418519220530954","@type":"Researcher","foaf:name":[{"@value":"Tom Gallagher"}],"role":"editor"}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"0022538X"},{"@type":"EISSN","@value":"10985514"}],"prism:publicationName":[{"@value":"Journal of Virology"}],"dc:publisher":[{"@value":"American Society for Microbiology"}],"prism:publicationDate":"2019-12","prism:volume":"93","prism:number":"24","prism:startingPage":"e01348-19"},"reviewed":"false","dc:rights":["https://journals.asm.org/non-commercial-tdm-license"],"url":[{"@id":"https://journals.asm.org/doi/pdf/10.1128/JVI.01348-19"}],"createdAt":"2019-09-30","modifiedAt":"2022-03-05","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360572092873407616","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Current status of potential therapeutic candidates for the COVID-19 crisis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360576137718072832","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review"}]},{"@id":"https://cir.nii.ac.jp/crid/1360869854341060736","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"3-Deazaguanosine inhibits SARS-CoV-2 viral replication and reduces the risk of COVID-19 pneumonia in hamster"}]},{"@id":"https://cir.nii.ac.jp/crid/1390583790037617792","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Synthesis of <i>N</i>-Hydroxycytidine and Dimethyl Dioxol Impurities, Method Development and Validation for Their Simultaneous Analysis in Molnupiravir"}]},{"@id":"https://cir.nii.ac.jp/crid/2050025942155225216","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Molecular mechanisms of the medicines for COVID-19"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1128/jvi.01348-19"},{"@type":"CROSSREF","@value":"10.1246/bcsj.20220179_references_DOI_BdCHDxIUkquPjKbwRlw2xcixQYB"},{"@type":"CROSSREF","@value":"10.1016/j.bbi.2020.04.046_references_DOI_BdCHDxIUkquPjKbwRlw2xcixQYB"},{"@type":"CROSSREF","@value":"10.1002/jmv.27730_references_DOI_BdCHDxIUkquPjKbwRlw2xcixQYB"},{"@type":"CROSSREF","@value":"10.1248/cpb.c24-00279_references_DOI_BdCHDxIUkquPjKbwRlw2xcixQYB"},{"@type":"CROSSREF","@value":"10.1016/j.isci.2025.112140_references_DOI_BdCHDxIUkquPjKbwRlw2xcixQYB"}]}