{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:27:35Z","timestamp":1789939655984,"version":"4.0.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Polyomavirus JC (JCV) replication causes progressive multifocal leukoencephalopathy (PML), a frequently fatal brain disease in immunodeficient patients, yet antiviral drugs are lacking. We characterized the lipid conjugate 1-\n            <jats:italic>O<\/jats:italic>\n            -hexadecyloxypropyl-cidofovir (CMX001) regarding JCV (Mad-4) replication in human brain progenitor-derived astrocytes (PDA) and the simian virus 40 (SV40) large-T-antigen-expressing COS-7 cells up to 7 days postinfection (dpi). We examined JCV loads by PCR, the infection rate by immunofluorescence, and host cell toxicity by WST-1 and BrdU incorporation assays. Supernatants from CMX001-treated PDA demonstrated a drug concentration-dependent decrease in JCV loads and infectivity. CMX001 had only a modest effect on host cell metabolism but reduced overall BrdU incorporation. In PDA at 7 dpi, the CMX001 50% effective concentration (EC\n            <jats:sub>50<\/jats:sub>\n            ) was 5.55 nM, the 50% cytotoxic concentration (CC\n            <jats:sub>50<\/jats:sub>\n            ) was 184.6 nM, and the 50% selectivity index (SI\n            <jats:sub>50<\/jats:sub>\n            ) was 33.3. The EC\n            <jats:sub>90<\/jats:sub>\n            was 19.7 nM, the CC\n            <jats:sub>90<\/jats:sub>\n            was 5,054 nM, and the SI\n            <jats:sub>90<\/jats:sub>\n            was 256.1. In COS-7 cells, JCV replication was faster and the EC\n            <jats:sub>50<\/jats:sub>\n            and EC\n            <jats:sub>90<\/jats:sub>\n            were 18- and 37-fold higher than those in PDA, i.e., 0.1 \u03bcM and 0.74 \u03bcM (CC\n            <jats:sub>50<\/jats:sub>\n            , 0.67 \u03bcM; SI\n            <jats:sub>50<\/jats:sub>\n            , 6.7; CC\n            <jats:sub>90<\/jats:sub>\n            , 12.2 \u03bcM; SI\n            <jats:sub>90<\/jats:sub>\n            , 16.5) at 5 dpi. We conclude that CMX001 inhibits JCV replication at concentrations\n            <jats:italic>in vitro<\/jats:italic>\n            that can be attained by oral administration without significant side effects in clinical studies.\n          <\/jats:p>","DOI":"10.1128\/aac.00046-11","type":"journal-article","created":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T18:53:46Z","timestamp":1300215226000},"page":"2129-2136","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["CMX001 (1-\n            <i>O<\/i>\n            -Hexadecyloxypropyl-Cidofovir) Inhibits Polyomavirus JC Replication in Human Brain Progenitor-Derived Astrocytes"],"prefix":"10.1128","volume":"55","author":[{"given":"Rainer","family":"Gosert","sequence":"first","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Hanssen","family":"Rinaldo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Control, University Hospital of North Norway, Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Wernli","sequence":"additional","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene O.","family":"Major","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans H.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland"},{"name":"Infectious Diseases &amp; Hospital Epidemiology, University Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199810000-00006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.587"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-1-78"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02269.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01614-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/147.4.676"},{"key":"e_1_3_2_8_2","first-page":"401","volume-title":"Laboratory diagnosis of viral infections","author":"Cinque P.","year":"2009","unstructured":"CinqueP. DumoulinA. HirschH. H.. 2009. Diagnosis of polyomavirus infection, replication and disease, p. 401\u2013424. In JeromeK. (ed.), Laboratory diagnosis of viral infections. Informa Healthcare, New York, NY."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.3.623"},{"key":"e_1_3_2_10_2","first-page":"917","volume-title":"Fundamental virology","author":"Cole C. N.","year":"1996","unstructured":"ColeC. N. 1996. Polyomavirinae: The viruses and their replication, p. 917\u2013945. In BernardD. M. K. FieldsN. HowleyPeter M. (ed.), Fundamental virology, 3rd ed. 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Agents Chemoth., Boston, MA, 12 to 15 September 2010."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3724-3733.2005"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000136093.47316.f3"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.148.3676.1477"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00046-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00046-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:29:18Z","timestamp":1645486158000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00046-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1128\/AAC.00046-11"],"URL":"https:\/\/doi.org\/10.1128\/aac.00046-11","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5]]},"assertion":[{"value":"2011-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}