{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:09:12Z","timestamp":1784192952932,"version":"3.55.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6878,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>The deoxyguanosine analog penciclovir (PCV; 9\u2013[4\u2013hydroxy\u20133\u2013hydroxymethyl\u2013but\u20131\u2013yl]guanine), has shown potent antiviral activity against herpes viruses and hepadnaviruses. Efficacy against chronic hepatitis B virus (HBV) infection has been demonstrated in an animal model and in recent clinical trials of famciclovir, the oral form of PCV. The antiviral activity of PCV is believed to be dependent on the intracellular formation of PCV\u2013triphosphate (PCV\u2013TP) which is presumed to inhibit HBV replication by interfering with viral DNA polymerase activity. The (<\/jats:bold>\n                                 <jats:bold>\n                                    S\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013enantiomer is preferentially formed in herpes virus\u2013infected cells, and is the more active against the herpes simplex virus; however, little is known about the biochemical mechanisms of PCV phosphorylation or of interference with viral replication in HBV\u2013infected cells. Here, we report that in contrast with herpes simplex virus, the (R)\u2013enantiomer of PCV\u2013TP is a more potent inhibitor of HBV DNA polymerase\u2013reverse transcriptase (pol\u2013RT) in vitro than the (<\/jats:bold>\n                                 <jats:bold>\n                                    S\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013enantiomer. In assays for HBV DNA pol\u2013RT activity, in which purified viral core particles were the enzyme source, the IC50s for (<\/jats:bold>\n                                 <jats:bold>\n                                    R\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013 and (<\/jats:bold>\n                                 <jats:bold>\n                                    S\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013enantiomers of PCV\u2013TP were 2.5 micromol\/L and 11 micromol\/L, respectively. The estimated Kis for (<\/jats:bold>\n                                 <jats:bold>\n                                    R\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013 and (<\/jats:bold>\n                                 <jats:bold>\n                                    S\n                                 <\/jats:bold>\n                                 <jats:bold>)\u2013 PCV\u2013TP were approximately 0.03 micromol\/L and approximately .04 micromol\/L, respectively, about 3\u2013fold lower than the Km for deoxyguanosine triphosphate (dGTP) in the same system. In addition, we report that PCV metabolism is similar in both control (HepG2) and in HBV\u2013transfected (2.2.15) hepatoblastoma cells<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>, indicating that cellular enzyme(s) catalyze PCV phosphorylation. Peak PCV\u2013TP concentrations of about .4 micromol\/L were reached in both cell types in less than 12 hours, and intracellular PCV\u2013TP was exceptionally stable with a half\u2013life of about 18 hours. These observations provide a mechanistic basis for the potent activity of PCV against HBV.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510240504","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T00:13:01Z","timestamp":1100218381000},"page":"996-1002","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":62,"title":["Inhibition of Hepatitis B Virus Dna Polymerase by Enantiomers of Penciclovir Triphosphate and Metabolic Basis for Selective Inhibition of Hbv Replication by Penciclovir"],"prefix":"10.1097","volume":"24","author":[{"given":"T","family":"Shaw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S S","family":"Mok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S A","family":"Locarnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510240504","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199611000-00004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:23:31Z","timestamp":1733052211000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199611000-00004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,11]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1996]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510240504","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1996,11]]}}}