{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:12:52Z","timestamp":1772809972036,"version":"3.50.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"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":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Like normal cellular nucleosides, the nucleoside reverse transcriptase (RT) inhibitor (NRTI) 4\u2032-ethynyl-2-fluoro-2\u2032-deoxyadenosine (EFdA) has a 3\u2032-hydroxyl moiety, and yet EFdA is a highly potent inhibitor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication with activity against a broad range of clinically important drug-resistant HIV isolates. We evaluated the anti-HIV activity of EFdA in primary human cells and in HIV-infected humanized mice. EFdA exhibited excellent potency against HIV\n            <jats:sub>JR-CSF<\/jats:sub>\n            in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs), with a 50% inhibitory concentration of 0.25 nM and a selectivity index of 184,000; similar antiviral potency was found against 12 different HIV clinical isolates from multiple clades (A, B, C, D, and CRF01_AE). EFdA was readily absorbed after oral dosing (5 mg\/kg of body weight) in both mice and the rhesus macaque, with micromolar levels of the maximum concentration of drug in serum (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) attained at 30 min and 90 min, respectively. Trough levels were at or above 90% inhibitory concentration (IC\n            <jats:sub>90<\/jats:sub>\n            ) levels in the macaque at 24 h, suggesting once-daily dosing. EFdA showed reasonable penetration of the blood-brain barrier in the rhesus macaque, with cerebrospinal fluid levels at approximately 25% of plasma levels 8 h after single oral dosing. Rhesus PBMCs isolated 24 h following a single oral dose of 5 mg\/kg EFdA were refractory to SIV infection due to sufficiently high intracellular EFdA-triphosphate levels. The intracellular half-life of EFdA-triphosphate in PBMCs was determined to be &gt;72 h following a single exposure to EFdA. Daily oral administration of EFdA at low dosage levels (1 to 10 mg\/kg\/day) was highly effective in protecting humanized mice from HIV infection, and 10 mg\/kg\/day oral EFdA completely suppressed HIV RNA to undetectable levels within 2 weeks of treatment.\n          <\/jats:p>","DOI":"10.1128\/aac.05036-14","type":"journal-article","created":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T01:51:20Z","timestamp":1430790680000},"page":"4190-4198","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["Oral Administration of the Nucleoside EFdA (4\u2032-Ethynyl-2-Fluoro-2\u2032-Deoxyadenosine) Provides Rapid Suppression of HIV Viremia in Humanized Mice and Favorable Pharmacokinetic Properties in Mice and the Rhesus Macaque"],"prefix":"10.1128","volume":"59","author":[{"given":"Cheryl A.","family":"Stoddart","sequence":"first","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofiya A.","family":"Galkina","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pheroze","family":"Joshi","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Kosikova","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose M.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Sloan","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron B.","family":"Reeve","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan G.","family":"Sarafianos","sequence":"additional","affiliation":[{"name":"Bond Life Sciences Center, Department of Molecular Microbiology &amp; Immunology, and Department of Biochemistry, University of Missouri, Columbia, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Murphey-Corb","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Parniak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2013.0262"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.036616"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00270-09"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.04.007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1081\/NCN-120022678"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00277-07"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/15257770701545218"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01703-13"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2697"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.755"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000655"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06676-11"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12180"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044664"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.10.4735-4742.1990"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/13.3.1015"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3646751"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.59.2.284-291.1986"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6089-6101.2005"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.3.1247-1249.2000"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.8.2557-2563.1999"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.8.2533-2537.1999"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/321435a0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098588802500609"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001251"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.3.783-786.2000"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00723-12"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.2.159"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06120-11"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.05036-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.05036-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:55:47Z","timestamp":1645484147000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.05036-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1128\/AAC.05036-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.05036-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7]]},"assertion":[{"value":"2014-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}