{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:22Z","timestamp":1793413702588,"version":"4.5.0"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Atea Pharmaceuticals","award":["AT-02A-001"],"award-info":[{"award-number":["AT-02A-001"]}],"id":[{"id":"https:\/\/ror.org\/00rezvm23","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic sensitivity was observed in Asian subjects, and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15\u201325 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the target\n                      <jats:italic>in vitro<\/jats:italic>\n                      90% effective concentration (EC\n                      <jats:sub>90<\/jats:sub>\n                      ) of 0.64 \u00b5M in inhibiting DENV replication, and maintained this level over the treatment period. The favorable safety and pharmacokinetic results support the evaluation of AT-752 as an antiviral for the treatment of dengue in future clinical studies.\n                    <\/jats:p>\n                    <jats:p>\n                      Registered at ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04722627\" xlink:type=\"simple\">NCT04722627<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01615-23","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T08:45:39Z","timestamp":1711356339000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7662-1616","authenticated-orcid":false,"given":"Xiao-Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Lickliter","sequence":"additional","affiliation":[{"name":"Nucleus Network, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Montrond","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ishak","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayle","family":"James","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Belanger","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Horga","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Hammond","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals Inc, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-819400-3.00016-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.07.026"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12080829"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.105"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed6040180"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40506-023-00263-w"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001831"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1658503"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2023.102598"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.572681"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis470"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000785"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ949"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70730-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-014-0590-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00988-21"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2023.105574"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02479-20"},{"key":"e_1_3_2_20_2","volume-title":"Guidance for industry estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers","author":"CDER","year":"2005","unstructured":"CDER. 2005. Guidance for industry estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1026451721686"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01615-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01615-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T09:04:29Z","timestamp":1714640669000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01615-23"}},"subtitle":[],"editor":[{"given":"Miguel Angel","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,2]]}},"alternative-id":["10.1128\/aac.01615-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01615-23","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.03.24300771","asserted-by":"object"}]},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"assertion":[{"value":"2023-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01615-23"}}