{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T03:49:26Z","timestamp":1777348166546,"version":"3.51.4"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA32779"],"award-info":[{"award-number":["R01 CA32779"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI019838"],"award-info":[{"award-number":["R01 AI019838"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R44 AI082799"],"award-info":[{"award-number":["R44 AI082799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005740","name":"Iowa Space Grant Consortium","doi-asserted-by":"publisher","award":["NASA NNX10AK63H"],"award-info":[{"award-number":["NASA NNX10AK63H"]}],"id":[{"id":"10.13039\/100005740","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cyclopropavir (CPV) is a promising antiviral drug against human cytomegalovirus (HCMV). As with ganciclovir (GCV), the current standard for HCMV treatment, activation of CPV requires multiple steps of phosphorylation and is enantioselective. We hypothesized that the resulting CPV triphosphate (CPV-TP) would stereoselectively target HCMV DNA polymerase and terminate DNA synthesis. To test this hypothesis, we synthesized both enantiomers of CPV-TP [(+) and (\u2212)] and investigated their action on HCMV polymerase. Both enantiomers inhibited HCMV polymerase competitively with dGTP, with (+)-CPV-TP exhibiting a more than 20-fold lower apparent\n            <jats:italic>\n              K\n              <jats:sub>i<\/jats:sub>\n            <\/jats:italic>\n            than (\u2212)-CPV-TP. Moreover, (+)-CPV-TP was a more potent inhibitor than GCV-TP. (+)-CPV-TP also exhibited substantially lower apparent\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            and somewhat higher apparent\n            <jats:italic>k<\/jats:italic>\n            <jats:sub>cat<\/jats:sub>\n            values than (\u2212)-CPV-TP and GCV-TP for incorporation into DNA by the viral polymerase. As is the case for GCV-TP, both CPV-TP enantiomers behaved as nonobligate chain terminators, with the polymerase terminating DNA synthesis after incorporation of one additional nucleotide. These results elucidate how CPV-TP acts on HCMV DNA polymerase and help explain why CPV is more potent against HCMV replication than GCV.\n          <\/jats:p>","DOI":"10.1128\/aac.00449-16","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T02:19:05Z","timestamp":1462241945000},"page":"4176-4182","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Potency and Stereoselectivity of Cyclopropavir Triphosphate Action on Human Cytomegalovirus DNA Polymerase"],"prefix":"10.1128","volume":"60","author":[{"given":"Han","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Microbiotix Inc., Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengwei","family":"Li","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Zemlicka","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian G.","family":"Gentry","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical, Biomedical and Administrative Sciences, College of Pharmacy and Health Sciences, Drake University, Des Moines, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry L.","family":"Bowlin","sequence":"additional","affiliation":[{"name":"Microbiotix Inc., Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Coen","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1075-8593(06)05003-9","volume-title":"Advances in antiviral drug design","author":"Zemlicka J","year":"2007","unstructured":"Zemlicka J. 2007. 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