{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:46:12Z","timestamp":1793191572606,"version":"4.5.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"},{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p> \u03b2-D-2\u2032-Deoxy-2\u2032-fluoro-2\u2032- 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 \u00b5M. 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\u2032- C-methyl adenosine and other 2\u2032-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 \u2265100 mg\/kg per day. <\/jats:p>","DOI":"10.1177\/095632020601700203","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T17:01:37Z","timestamp":1426525297000},"page":"79-87","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":112,"title":["Inhibition of Hepatitis C Replicon RNA Synthesis by \u03b2-D-2\u2032-deoxy-2\u2032-fluoro-2\u2032-<i>C<\/i>-Methylcytidine: A Specific Inhibitor of Hepatitis C Virus Replication"],"prefix":"10.1177","volume":"17","author":[{"given":"Lieven J","family":"Stuyver","sequence":"first","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara R","family":"McBrayer","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip M","family":"Tharnish","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Clark","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Hollecker","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Lostia","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Nachman","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Grier","sequence":"additional","affiliation":[{"name":"School of Medicine\/Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Bennett","sequence":"additional","affiliation":[{"name":"School of Medicine\/Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yu","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine\/Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F","family":"Schinazi","sequence":"additional","affiliation":[{"name":"School of Medicine\/Veterans Affairs Medical Center, Decatur, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Morrey","sequence":"additional","affiliation":[{"name":"Utah State University, Logan, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L","family":"Julander","sequence":"additional","affiliation":[{"name":"Utah State University, Logan, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A","family":"Furman","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Otto","sequence":"additional","affiliation":[{"name":"Pharmasset Inc, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,4,1]]},"reference":[{"key":"bibr1-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908193410802"},{"key":"bibr2-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1016\/0166-3542(94)90089-2"},{"key":"bibr3-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5498.1972"},{"key":"bibr4-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210914200"},{"key":"bibr5-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1021\/jm0502788"},{"key":"bibr6-095632020601700203","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200115040-00003"},{"key":"bibr7-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60539-3"},{"key":"bibr8-095632020601700203","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.02.009"},{"key":"bibr9-095632020601700203","unstructured":"Devos R, Jiang R, Martin JA, Merrett JH, Najera I, Shimma N & Tsukuda T (2002) 4\u2032-substituted nucleosides. 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