{"@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/1363670318770185472.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1177/095632020601700203"}},{"identifier":{"@type":"URI","@value":"https://journals.sagepub.com/doi/pdf/10.1177/095632020601700203"}}],"dc:title":[{"@value":"Inhibition of Hepatitis C Replicon RNA Synthesis by β-D-2′-deoxy-2′-fluoro-2′-<i>C</i>-Methylcytidine: A Specific Inhibitor of Hepatitis C Virus Replication"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p> β-D-2′-Deoxy-2′-fluoro-2′- C-methylcytidine (PSI-6130) is a cytidine analogue with potent and selective anti-hepatitis C virus (HCV) activity in the subgenomic HCV replicon assay, 90% effective concentration (EC<jats:sub>90</jats:sub>)=4.6 +2.0 µM. The spectrum of activity and cytotoxicity profile of PSI-6130 was evaluated against a diverse panel of viruses and cell types, and against two additional HCV-1b replicons. The S282T mutation, which confers resistance to 2′- C-methyl adenosine and other 2′-methylated nucleosides, showed only a 6.5-fold increase in EC<jats:sub>90</jats:sub>. When assayed for activity against bovine diarrhoea virus (BVDV), which is typically used as a surrogate assay to identify compounds active against HCV, PSI-6130 showed no anti-BVDV activity. Weak antiviral activity was noted against other flaviviruses, including West Nile virus, Dengue type 2, and yellow fever virus. These results indicate that PSI-6130 is a specific inhibitor of HCV. PSI-6130 showed little or no cytotoxicity against various cell types, including human peripheral blood mononuclear and human bone marrow progenitor cells. No mitochondrial toxicity was observed with PSI-6130. The reduced activity against the RdRp S282T mutant suggests that PSI-6130 is an inhibitor of replicon RNA synthesis. Finally, the no-effect dose for mice treated intraperitoneally with PSI-6130 for six consecutive days was ≥100 mg/kg per day. </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670318770185472","@type":"Researcher","foaf:name":[{"@value":"Lieven J Stuyver"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185483","@type":"Researcher","foaf:name":[{"@value":"Tamara R McBrayer"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185344","@type":"Researcher","foaf:name":[{"@value":"Phillip M Tharnish"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185479","@type":"Researcher","foaf:name":[{"@value":"Jeremy Clark"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185473","@type":"Researcher","foaf:name":[{"@value":"Laurent Hollecker"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185475","@type":"Researcher","foaf:name":[{"@value":"Stefania Lostia"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185477","@type":"Researcher","foaf:name":[{"@value":"Tammy Nachman"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185346","@type":"Researcher","foaf:name":[{"@value":"Jason Grier"}],"jpcoar:affiliationName":[{"@value":"School of Medicine/Veterans Affairs Medical Center, Decatur, GA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185474","@type":"Researcher","foaf:name":[{"@value":"Matthew A Bennett"}],"jpcoar:affiliationName":[{"@value":"School of Medicine/Veterans Affairs Medical Center, Decatur, GA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185478","@type":"Researcher","foaf:name":[{"@value":"Meng-Yu Xie"}],"jpcoar:affiliationName":[{"@value":"School of Medicine/Veterans Affairs Medical Center, Decatur, GA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185345","@type":"Researcher","foaf:name":[{"@value":"Raymond F Schinazi"}],"jpcoar:affiliationName":[{"@value":"School of Medicine/Veterans Affairs Medical Center, Decatur, GA, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185482","@type":"Researcher","foaf:name":[{"@value":"John D Morrey"}],"jpcoar:affiliationName":[{"@value":"Utah State University, Logan, UT, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185480","@type":"Researcher","foaf:name":[{"@value":"Justin L Julander"}],"jpcoar:affiliationName":[{"@value":"Utah State University, Logan, UT, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185481","@type":"Researcher","foaf:name":[{"@value":"Phillip A Furman"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318770185476","@type":"Researcher","foaf:name":[{"@value":"Michael J Otto"}],"jpcoar:affiliationName":[{"@value":"Pharmasset Inc, Princeton, NJ, USA"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"09563202"},{"@type":"EISSN","@value":"20402066"}],"prism:publicationName":[{"@value":"Antiviral Chemistry and Chemotherapy"}],"dc:publisher":[{"@value":"SAGE 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