{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T20:25:05Z","timestamp":1787257505423,"version":"build-2736575974"},"reference-count":94,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013200","name":"Government of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U19AI171443-01"],"award-info":[{"award-number":["1U19AI171443-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.jbc.2026.113316","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:06:15Z","timestamp":1783350375000},"page":"113316","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Substrate and target selectivity of 4\u2032-fluoroadenosine against viral and host polymerases"],"prefix":"10.1016","volume":"302","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7231-0663","authenticated-orcid":false,"given":"Simon M.","family":"Walker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5208-6534","authenticated-orcid":false,"given":"Arlo J.","family":"Loutan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egor P.","family":"Tchesnokov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Kocincova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-6201","authenticated-orcid":false,"given":"Calvin J.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby A.","family":"Escobedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7918-0395","authenticated-orcid":false,"given":"Olivia A.","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5919-6746","authenticated-orcid":false,"given":"Kim","family":"Morsheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3910-6454","authenticated-orcid":false,"given":"Suncheol","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-359X","authenticated-orcid":false,"given":"Anant","family":"Gharpure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ixchel","family":"Urbano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Heacock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushboo","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C.","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Huerta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3337-6528","authenticated-orcid":false,"given":"Malina A.","family":"Bakowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2414-7341","authenticated-orcid":false,"given":"Laura","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil K.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyan","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-0804","authenticated-orcid":false,"given":"Luis","family":"Martinez-Sobrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-425X","authenticated-orcid":false,"given":"Christopher F.","family":"Basler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Davey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Chanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab K.","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-5806","authenticated-orcid":false,"given":"Matthias","family":"G\u00f6tte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2026.113316_bib1","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1093\/cid\/ciaf476","article-title":"The indispensable value of small-molecule antivirals in epidemic and pandemic preparedness","volume":"82","author":"Draghia-Akli","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.jbc.2026.113316_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/v10020076","article-title":"RNA dependent RNA polymerases: insights from structure, function and evolution","volume":"10","author":"Venkataraman","year":"2018","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib4","first-page":"109","article-title":"Broad spectrum antiviral nucleosides-our best hope for the future","volume":"57","author":"Seley-Radtke","year":"2021","journal-title":"Annu. Rep. Med. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved antiviral drugs over the past 50 years","volume":"29","author":"De Clercq","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.jbc.2026.113316_bib6","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3390\/v11080745","article-title":"A comprehensive superposition of viral polymerase structures","volume":"11","author":"Peersen","year":"2019","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib7","doi-asserted-by":"crossref","first-page":"6851","DOI":"10.3390\/cimb45080433","article-title":"Recent advances in molecular mechanisms of nucleoside antivirals","volume":"45","author":"Kamzeeva","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"10.1016\/j.jbc.2026.113316_bib8","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1056\/NEJMoa1910993","article-title":"A randomized, controlled trial of Ebola virus disease therapeutics","volume":"381","author":"Mulangu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jbc.2026.113316_bib10","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1038\/s41598-023-29517-9","article-title":"Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro","volume":"13","author":"Radoshitzky","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2026.113316_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/srep43395","article-title":"GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and paramyxoviruses","volume":"7","author":"Lo","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2026.113316_bib12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3390\/v18020257","article-title":"1\u2032- and 4\u2032-Cyano modified adenosine analogs against Prototypic Flavivirus RNA-Dependent RNA polymerases","volume":"18","author":"Walker","year":"2026","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.107940","article-title":"Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice","volume":"32","author":"Pruijssers","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2026.113316_bib14","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1038\/s41467-020-19055-7","article-title":"A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19","volume":"11","author":"Xie","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2026.113316_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2025.106186","article-title":"Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo","volume":"239","author":"Verwimp","year":"2025","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41586-021-03312-w","article-title":"SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801","volume":"591","author":"Wahl","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2026.113316_bib17","doi-asserted-by":"crossref","first-page":"eabb5883","DOI":"10.1126\/scitranslmed.abb5883","article-title":"An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice","volume":"12","author":"Sheahan","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.jbc.2026.113316_bib18","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00766-18","article-title":"Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses","volume":"62","author":"Yoon","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib19","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02395-16","article-title":"Characterization of beta-d-N(4)-Hydroxycytidine as a novel inhibitor of Chikungunya virus","volume":"61","author":"Ehteshami","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib20","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.3390\/v7122934","article-title":"Identification of a new ribonucleoside inhibitor of Ebola virus replication","volume":"7","author":"Reynard","year":"2015","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib21","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1128\/AAC.47.1.244-254.2003","article-title":"Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture","volume":"47","author":"Stuyver","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2022.105453","article-title":"The prophylactic and therapeutic efficacy of the broadly active antiviral ribonucleoside N(4)-Hydroxycytidine (EIDD-1931) in a mouse model of lethal Ebola virus infection","volume":"209","author":"Bluemling","year":"2023","journal-title":"Antivir. Res"},{"key":"10.1016\/j.jbc.2026.113316_bib24","doi-asserted-by":"crossref","DOI":"10.1093\/narmme\/ugaf041","article-title":"Inhibitory effects of molnupiravir on Crimean-Congo hemorrhagic fever virus polymerase","volume":"3","author":"Sloan","year":"2026","journal-title":"NAR Mol. Med."},{"key":"10.1016\/j.jbc.2026.113316_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2024.106046","article-title":"Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4'-fluorouridine","volume":"233","author":"Schrell","year":"2025","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib26","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.ado7034","article-title":"Delayed low-dose oral administration of 4'-fluorouridine inhibits pathogenic arenaviruses in animal models of lethal disease","volume":"16","author":"Welch","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.jbc.2026.113316_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011993","article-title":"Influenza A virus resistance to 4'-fluorouridine coincides with viral attenuation in vitro and in vivo","volume":"20","author":"Lieber","year":"2024","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib28","article-title":"The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase","volume":"68","author":"Chen","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib29","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011342","article-title":"4'-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses","volume":"19","author":"Lieber","year":"2023","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1126\/science.abj5508","article-title":"4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication","volume":"375","author":"Sourimant","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.jbc.2026.113316_bib31","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00420-24","article-title":"4'-Fluorouridine inhibits alphavirus replication and infection in vitro and in vivo","volume":"15","author":"Yin","year":"2024","journal-title":"mBio"},{"key":"10.1016\/j.jbc.2026.113316_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2025.106114","article-title":"Effectiveness of nucleoside analogs against Wetland virus infection","volume":"236","author":"Wang","year":"2025","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1014093","article-title":"Efficacy of the nucleoside analog 4'-Fluorouridine against Nipah virus in the Syrian hamster model","volume":"22","author":"Escaffre","year":"2026","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2022.105501","article-title":"Kill or corrupt: mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2","volume":"210","author":"Shannon","year":"2023","journal-title":"Antivir. Res"},{"key":"10.1016\/j.jbc.2026.113316_bib35","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1016\/j.bmcl.2012.02.105","article-title":"Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides","volume":"22","author":"Cho","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.jbc.2026.113316_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107514","article-title":"Mechanism and spectrum of inhibition of a 4'-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses","volume":"300","author":"Gordon","year":"2024","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.101529","article-title":"Efficient incorporation and template-dependent polymerase inhibition are major determinants for the broad-spectrum antiviral activity of remdesivir","volume":"298","author":"Gordon","year":"2022","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib38","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1128\/AAC.02666-14","article-title":"Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase","volume":"58","author":"Fung","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008283","article-title":"Independent inhibition of the polymerase and deubiquitinase activities of the Crimean-Congo Hemorrhagic Fever Virus full-length L-protein","volume":"14","author":"Tchesnokov","year":"2020","journal-title":"Plos Negl. Trop. Dis."},{"key":"10.1016\/j.jbc.2026.113316_bib40","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3390\/v11040326","article-title":"Mechanism of inhibition of Ebola virus RNA-Dependent RNA polymerase by remdesivir","volume":"11","author":"Tchesnokov","year":"2019","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib41","doi-asserted-by":"crossref","first-page":"16156","DOI":"10.1074\/jbc.AC120.015720","article-title":"Template-dependent inhibition of coronavirus RNA-dependent RNA polymerase by remdesivir reveals a second mechanism of action","volume":"295","author":"Tchesnokov","year":"2020","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib42","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1126\/science.abc1560","article-title":"Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir","volume":"368","author":"Yin","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.jbc.2026.113316_bib43","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41586-022-05664-3","article-title":"Structural basis for substrate selection by the SARS-CoV-2 replicase","volume":"614","author":"Malone","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2026.113316_bib44","article-title":"Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases","volume":"120","author":"Wu","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.jbc.2026.113316_bib45","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41594-019-0232-z","article-title":"Structural snapshots of actively transcribing influenza polymerase","volume":"26","author":"Kouba","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.jbc.2026.113316_bib46","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1074\/jbc.RA120.013679","article-title":"Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency","volume":"295","author":"Gordon","year":"2020","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib47","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41467-020-20542-0","article-title":"Mechanism of SARS-CoV-2 polymerase stalling by remdesivir","volume":"12","author":"Kokic","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2026.113316_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109882","article-title":"Remdesivir overcomes the S861 roadblock in SARS-CoV-2 polymerase elongation complex","volume":"37","author":"Wu","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2026.113316_bib49","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.antiviral.2017.04.005","article-title":"Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs","volume":"143","author":"Jin","year":"2017","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib50","doi-asserted-by":"crossref","first-page":"14711","DOI":"10.1021\/bi035596s","article-title":"Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase","volume":"42","author":"Lee","year":"2003","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2026.113316_bib51","doi-asserted-by":"crossref","first-page":"40847","DOI":"10.1074\/jbc.M106743200","article-title":"Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase","volume":"276","author":"Johnson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib52","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003030","article-title":"Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides","volume":"8","author":"Arnold","year":"2012","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib53","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s40265-014-0247-z","article-title":"Sofosbuvir: a review of its use in patients with chronic hepatitis C","volume":"74","author":"Keating","year":"2014","journal-title":"Drugs"},{"key":"10.1016\/j.jbc.2026.113316_bib55","doi-asserted-by":"crossref","first-page":"e01719","DOI":"10.1128\/AAC.01719-19","article-title":"Analysis of the potential for N(4)-Hydroxycytidine to inhibit mitochondrial replication and function","volume":"64","author":"Sticher","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib56","doi-asserted-by":"crossref","first-page":"7077","DOI":"10.1128\/AAC.01253-16","article-title":"Antiviral nucleotide incorporation by recombinant human mitochondrial RNA polymerase is predictive of increased in vivo mitochondrial toxicity risk","volume":"60","author":"Fenaux","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib57","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1128\/AAC.01922-15","article-title":"Role of mitochondrial RNA polymerase in the toxicity of nucleotide inhibitors of hepatitis C virus","volume":"60","author":"Feng","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib58","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1016\/j.molcel.2025.07.002","article-title":"Human mitochondrial RNA polymerase structures reveal transcription start site and slippage mechanism","volume":"85","author":"Shen","year":"2025","journal-title":"Mol. Cell"},{"key":"10.1016\/j.jbc.2026.113316_bib59","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0079-6107(01)00014-1","article-title":"Structure and function of the radical enzyme ribonucleotide reductase","volume":"77","author":"Eklund","year":"2001","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"10.1016\/j.jbc.2026.113316_bib60","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/infdis\/jiab247","article-title":"beta-d-N4-hydroxycytidine inhibits SARS-CoV-2 through lethal mutagenesis but is also mutagenic to Mammalian cells","volume":"224","author":"Zhou","year":"2021","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.jbc.2026.113316_bib61","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0149-2918(00)80064-8","article-title":"Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity","volume":"22","author":"Moyle","year":"2000","journal-title":"Clin. Ther."},{"key":"10.1016\/j.jbc.2026.113316_bib62","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1089\/088922299310692","article-title":"Intracellular activation of 2',3'-dideoxyinosine and drug interactions in vitro","volume":"15","author":"Kewn","year":"1999","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"10.1016\/j.jbc.2026.113316_bib63","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0149-2918(00)90004-3","article-title":"Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity","volume":"22","author":"Kakuda","year":"2000","journal-title":"Clin. Ther."},{"key":"10.1016\/j.jbc.2026.113316_bib64","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2165\/00003088-200443090-00003","article-title":"Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics","volume":"43","author":"Kearney","year":"2004","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.jbc.2026.113316_bib65","doi-asserted-by":"crossref","DOI":"10.1093\/narmme\/ugaf029","article-title":"Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-beta-fluoro-4'-azidocytidine or azvudine","volume":"2","author":"Lee","year":"2025","journal-title":"NAR Mol. Med."},{"key":"10.1016\/j.jbc.2026.113316_bib66","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004995","article-title":"Molecular basis for the selective inhibition of respiratory syncytial virus RNA polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine triphosphate","volume":"11","author":"Deval","year":"2015","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib67","doi-asserted-by":"crossref","first-page":"9274","DOI":"10.1073\/pnas.1605223113","article-title":"Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA)","volume":"113","author":"Salie","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.jbc.2026.113316_bib68","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1021\/jm801595c","article-title":"The design, synthesis, and antiviral activity of monofluoro and difluoro analogues of 4'-azidocytidine against hepatitis C virus replication: the discovery of 4'-azido-2'-deoxy-2'-fluorocytidine and 4'-azido-2'-dideoxy-2',2'-difluorocytidine","volume":"52","author":"Smith","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib69","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1016\/j.bmcl.2007.02.004","article-title":"Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479","volume":"17","author":"Smith","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.jbc.2026.113316_bib70","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3851\/IMP1400","article-title":"Anti-hepatitis C virus activity of novel beta-d-2'-C-methyl-4'-azido pyrimidine nucleoside phosphoramidate prodrugs","volume":"20","author":"Rondla","year":"2009","journal-title":"Antivir. Chem. Chemother."},{"key":"10.1016\/j.jbc.2026.113316_bib71","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1074\/jbc.M708929200","article-title":"2'-deoxy-4'-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2'-alpha-hydroxyl groups","volume":"283","author":"Klumpp","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib72","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1021\/jm5017279","article-title":"Discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection","volume":"58","author":"Wang","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib73","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1021\/acs.jmedchem.6b01594","article-title":"Discovery and synthesis of a phosphoramidate prodrug of a Pyrrolo[2,1-f][triazin-4-amino] adenine C-Nucleoside (GS-5734) for the treatment of Ebola and emerging viruses","volume":"60","author":"Siegel","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib74","doi-asserted-by":"crossref","first-page":"35681","DOI":"10.1074\/jbc.M109.036616","article-title":"Mechanism of inhibition of HIV-1 reverse transcriptase by 4'-Ethynyl-2-fluoro-2'-deoxyadenosine triphosphate, a translocation-defective reverse transcriptase inhibitor","volume":"284","author":"Michailidis","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113316_bib75","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.molcel.2006.11.024","article-title":"Initiation and beyond: multiple functions of the human mitochondrial transcription machinery","volume":"24","author":"Bonawitz","year":"2006","journal-title":"Mol. Cell"},{"key":"10.1016\/j.jbc.2026.113316_bib76","series-title":"Inventors; 4\u2019-Substituted nucleosides and nucleotides as antiviral agents. WO 2024\/227159 A2","author":"Yu","year":"2024"},{"key":"10.1016\/j.jbc.2026.113316_bib77","first-page":"526","article-title":"[Synthesis and biological properties of pyrimidine 4'-fluoro nucleosides and 4'-fluoro uridine 5'-O-triphospate]","volume":"36","author":"Ivanov","year":"2010","journal-title":"Bioorg. Khim"},{"key":"10.1016\/j.jbc.2026.113316_bib78","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3390\/v8030071","article-title":"The iminosugar UV-4 is a broad inhibitor of influenza A and B viruses ex vivo and in mice","volume":"8","author":"Warfield","year":"2016","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib79","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1021\/acsinfecdis.5b00053","article-title":"High-Throughput minigenome System for identifying small-molecule inhibitors of Ebola virus replication","volume":"1","author":"Edwards","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"10.1016\/j.jbc.2026.113316_bib80","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.antiviral.2017.10.008","article-title":"Identification of 2'-deoxy-2'-fluorocytidine as a potent inhibitor of Crimean-Congo hemorrhagic fever virus replication using a recombinant fluorescent reporter virus","volume":"147","author":"Welch","year":"2017","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004879","article-title":"Recovery of recombinant Crimean Congo hemorrhagic fever virus reveals a function for non-structural glycoproteins cleavage by Furin","volume":"11","author":"Bergeron","year":"2015","journal-title":"Plos Pathog."},{"key":"10.1016\/j.jbc.2026.113316_bib82","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.antiviral.2013.07.018","article-title":"New-generation screening assays for the detection of anti-influenza compounds targeting viral and host functions","volume":"100","author":"Beyleveld","year":"2013","journal-title":"Antivir. Res."},{"key":"10.1016\/j.jbc.2026.113316_bib83","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41586-023-06947-z","article-title":"Structures, functions and adaptations of the human LINE-1 ORF2 protein","volume":"626","author":"Baldwin","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2026.113316_bib84","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1038\/s41598-018-22328-3","article-title":"Recombinant RNA-Dependent RNA polymerase complex of Ebola virus","volume":"8","author":"Tchesnokov","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2026.113316_bib85","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/s41467-024-45842-7","article-title":"Structure of the recombinant RNA polymerase from African Swine Fever Virus","volume":"15","author":"Pilotto","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2026.113316_bib86","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41586-019-1530-7","article-title":"Structures of influenza A virus RNA polymerase offer insight into viral genome replication","volume":"573","author":"Fan","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.jbc.2026.113316_bib87","doi-asserted-by":"crossref","first-page":"E2564","DOI":"10.1073\/pnas.1604935113","article-title":"biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes","volume":"113","author":"Weissmann","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.jbc.2026.113316_bib88","article-title":"MultiBac: multigene baculovirus-based eukaryotic protein complex production","volume":"5","author":"Bieniossek","year":"2008","journal-title":"Curr. Protoc. Protein Sci. Chapter"},{"key":"10.1016\/j.jbc.2026.113316_bib89","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/nbt1036","article-title":"Baculovirus expression system for heterologous multiprotein complexes","volume":"22","author":"Berger","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jbc.2026.113316_bib90","doi-asserted-by":"crossref","DOI":"10.3390\/v17030420","article-title":"Bunyaviral cap-snatching endonuclease activity and inhibition with Baloxavir-like inhibitors in the context of full-length L proteins","volume":"17","author":"Loutan","year":"2025","journal-title":"Viruses"},{"key":"10.1016\/j.jbc.2026.113316_bib91","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nmeth.4169","article-title":"cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination","volume":"14","author":"Punjani","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2026.113316_bib92","doi-asserted-by":"crossref","first-page":"e12719","DOI":"10.7554\/eLife.17219","article-title":"Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta","volume":"5","author":"Wang","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.jbc.2026.113316_bib93","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1002\/pro.3791","article-title":"Current developments in Coot for macromolecular model building of Electron Cryo-microscopy and Crystallographic Data","volume":"29","author":"Casanal","year":"2020","journal-title":"Protein Sci."},{"key":"10.1016\/j.jbc.2026.113316_bib94","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1107\/S2059798318006551","article-title":"Real-space refinement in PHENIX for cryo-EM and crystallography","volume":"74","author":"Afonine","year":"2018","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"10.1016\/j.jbc.2026.113316_bib95","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nmeth.3541","article-title":"EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy","volume":"12","author":"Barad","year":"2015","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2026.113316_bib96","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: more and better reference data for improved all-atom structure validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"10.1016\/j.jbc.2026.113316_bib97","doi-asserted-by":"crossref","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"key":"10.1016\/j.jbc.2026.113316_bib98","series-title":"The PyMOL Molecular Graphics System","author":"Schrodinger","year":"2015"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826021885?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826021885?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:45:01Z","timestamp":1787255101000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925826021885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":94,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S0021925826021885"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2026.113316","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Substrate and target selectivity of 4\u2032-fluoroadenosine against viral and host polymerases","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2026.113316","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"113316"}}