{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T05:47:06Z","timestamp":1782107226623,"version":"3.54.5"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Xanthine oxidase (XO) inhibitors remain the standard pharmacologic therapy for hyperuricemia. However, additional enzymatic components of the purine degradation pathway may contribute to uric acid synthesis. Guanine deaminase (GD) catalyzes the conversion of guanine to xanthine, providing substrate for downstream oxidation by XO. Cyclovir antivirals (acyclovir, valacyclovir, and famciclovir) are guanine nucleoside analogues that function as alternative substrates for GD and may influence urate production through substrate\u2010level interactions. We conducted retrospective analyses using two independent real\u2010world data sources: the Merative MarketScan Research Databases with linked laboratory data and the US Veterans Health Administration. Patients exposed to cyclovir antivirals were compared with untreated controls with herpes simplex virus infection. The primary outcome was serum uric acid (sUA) measured approximately 1\u2009year after index. Multivariable linear regression and inverse probability weighting were used to estimate adjusted differences in follow\u2010up sUA. In the MarketScan cohort, associations were most pronounced among patients with elevated baseline sUA (\u2265\u20096.8\u2009mg\/dL), with inverse probability\u2013weighted analyses demonstrating an adjusted difference of \u22120.87\u2009mg\/dL (95% CI: \u22121.59 to \u22120.14;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02). In the Veterans Health Administration cohort, cyclovir treatment was associated with an adjusted difference of \u22120.87\u2009mg\/dL (95% CI: \u22121.43 to \u22120.30;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003). Cyclovir antiviral exposure was associated with modest reductions in serum uric acid in two independent real\u2010world populations. Further mechanistic and prospective studies are warranted to clarify the role of GD and related pathway components in urate regulation.\n                  <\/jats:p>","DOI":"10.1111\/cts.70582","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:39:49Z","timestamp":1779925189000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Purine Analog Antivirals to Modulate Serum Uric Acid: Evidence From Real\u2010World Data"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-0097","authenticated-orcid":false,"given":"Joseph","family":"Magagnoli","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Center for Outcomes Research and Evaluation (CORE) College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy H.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Center for Outcomes Research and Evaluation (CORE) College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Campbell","family":"McInnes","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayakrishna","family":"Ambati","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Pathology University of Virginia School of Medicine  Charlottesville USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-6178","authenticated-orcid":false,"given":"S. Scott","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Center for Outcomes Research and Evaluation (CORE) College of Pharmacy University of South Carolina  Columbia South Carolina USA"},{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010143\u20107\u2010200510040\u201000009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/21501319231167379"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0306\u20104522(01)00352\u20109"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.9b00341"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20108981(84)90103\u20107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770008045444"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.07.054"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037724"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26740"},{"key":"e_1_2_10_11_1","unstructured":"Department of Veterans Affairs \u201cVA Informatics and Computing Infrastructure (VINCI) 2025\u201d https:\/\/www.research.va.gov\/programs\/vinci\/default.cfm."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20102107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2011.11.2511"},{"key":"e_1_2_10_14_1","first-page":"2281","volume-title":"Arthritis and Allied Conditions","author":"Becker M. A.","year":"2001"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70582","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:53:18Z","timestamp":1782103998000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/cts.70582"],"URL":"https:\/\/doi.org\/10.1111\/cts.70582","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"2025-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70582"}}