{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:57:07Z","timestamp":1784001427533,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013970","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000}}],"reference-count":123,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1R01AI150246, RO1AI140539, R01AI152362"],"award-info":[{"award-number":["1R01AI150246, RO1AI140539, R01AI152362"]}]},{"name":"NIH","award":["R01AI143850"],"award-info":[{"award-number":["R01AI143850"]}]},{"name":"NIH","award":["T32GM144302"],"award-info":[{"award-number":["T32GM144302"]}]},{"name":"CAMPP Antiviral Drug Discovery (AViDD) Center","award":["U19AI17144"],"award-info":[{"award-number":["U19AI17144"]}]},{"name":"Burroughs Wellcome Investigators","award":["Pathogenesis of Infectious Disease Award"],"award-info":[{"award-number":["Pathogenesis of Infectious Disease Award"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active against DENV2 were screened against all four serotypes. Since flaviviruses including West Nile virus and Zika virus are also important human pathogens, we screened these compounds for activity and identified compounds that were broadly active in these cellular and viral models. We further evaluated antivirals in primary human keratinocytes and fibroblasts, which are early targets of mosquito-transmitted DENV infection. From this screen, we identified 23 nucleoside analogs with broad antiviral activity against DENV and focused on two purine analogs UPGNUC255 and UPGNUC558, that demonstrated potent pan-flaviviral activity achieving &gt;10-fold viral load reduction across all four DENV serotypes and other flaviviruses across cell models. Mechanistic studies revealed that both compounds target the viral RNA-dependent RNA polymerase (RdRp) domain of NS5. Resistance to UPGNUC558 was associated with a conserved S604T substitution, conferring cross-resistance to other 2\u2032C-substituted nucleoside analogs. Resistance to UPGNUC255 was linked to a previously unknown R355Q mutation, located near the catalytic GDD motif of RdRp. These findings highlight UPGNUC255 and UPGNUC558 as promising leads for the development of broad-spectrum antiviral agents against flaviviruses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013970","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T18:35:45Z","timestamp":1771353345000},"page":"e1013970","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["NS5-targeting nucleoside analogs inhibit dengue virus and other flaviviruses"],"prefix":"10.1371","volume":"22","author":[{"given":"Priyanka","family":"Bhakt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swechha 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K.","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Ramage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-6610","authenticated-orcid":true,"given":"Sara","family":"Cherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"issue":"528","key":"ppat.1013970.ref001","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aax4144","article-title":"Mapping global variation in dengue transmission intensity","volume":"12","author":"L Cattarino","year":"2020","journal-title":"Sci Transl 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Duangkhae","year":"2018","journal-title":"J Invest Dermatol"},{"issue":"5","key":"ppat.1013970.ref031","doi-asserted-by":"crossref","DOI":"10.1016\/j.jid.2023.09.287","article-title":"Dengue Virus Infects Human Skin Langerhans Cells through Langerin for Dissemination to Dendritic Cells","volume":"144","author":"LC Helgers","year":"2024","journal-title":"J Invest Dermatol"},{"issue":"12","key":"ppat.1013970.ref032","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.3390\/v11121136","article-title":"Insight into the Tropism of Dengue Virus in Humans","volume":"11","author":"F Begum","year":"2019","journal-title":"Viruses"},{"issue":"33","key":"ppat.1013970.ref033","doi-asserted-by":"crossref","first-page":"17437","DOI":"10.1074\/jbc.M116.724013","article-title":"Identification of a Conserved RNA-dependent RNA Polymerase (RdRp)-RNA Interface Required for Flaviviral Replication","volume":"291","author":"K Hodge","year":"2016","journal-title":"J Biol 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Yin","year":"2020","journal-title":"Science"},{"issue":"20","key":"ppat.1013970.ref040","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":"CJ Gordon","year":"2020","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1013970.ref041","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3390\/v10090453","article-title":"Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus","volume":"10","author":"J-C Saiz","year":"2018","journal-title":"Viruses"},{"issue":"5","key":"ppat.1013970.ref042","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1002\/med.21664","article-title":"Medicinal chemistry strategies toward host targeting antiviral agents","volume":"40","author":"X Ji","year":"2020","journal-title":"Med Res 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Tick-Borne Flavivirus from 2\u2019-C-Methylated Nucleoside Antivirals Is Mediated by a Single Conservative Mutation in NS5 That Has a Dramatic Effect on Viral Fitness","volume":"91","author":"L Eyer","year":"2017","journal-title":"J Virol"},{"key":"ppat.1013970.ref067","doi-asserted-by":"crossref","first-page":"164878","DOI":"10.1155\/2010\/164878","article-title":"Cells in dengue virus infection in vivo","volume":"2010","author":"S Noisakran","year":"2010","journal-title":"Adv Virol"},{"issue":"6","key":"ppat.1013970.ref068","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.humpath.2014.01.022","article-title":"Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar","volume":"45","author":"KS Aye","year":"2014","journal-title":"Hum Pathol"},{"issue":"3","key":"ppat.1013970.ref069","doi-asserted-by":"crossref","first-page":"416","DOI":"10.4269\/ajtmh.2009.80.416","article-title":"Tropism of dengue virus in mice and humans defined by viral 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Meertens","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ppat.1013970.ref073","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.antiviral.2016.07.018","article-title":"Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus","volume":"133","author":"L Eyer","year":"2016","journal-title":"Antiviral Res"},{"issue":"1","key":"ppat.1013970.ref074","article-title":"Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus","volume":"15","author":"SS Good","year":"2020","journal-title":"PLoS ONE"},{"issue":"3","key":"ppat.1013970.ref075","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1128\/JVI.79.3.1943-1947.2005","article-title":"The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase","volume":"79","author":"P Leyssen","year":"2005","journal-title":"J Virol"},{"issue":"1","key":"ppat.1013970.ref076","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0166-3542(02)00185-7","article-title":"Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses","volume":"58","author":"JM Crance","year":"2003","journal-title":"Antiviral Res"},{"issue":"3","key":"ppat.1013970.ref077","article-title":"Mechanism and spectrum of inhibition of viral polymerases by 2\u2019-deoxy-2\u2019-\u03b2-fluoro-4\u2019-azidocytidine or azvudine","volume":"2","author":"HW Lee","year":"2025","journal-title":"NAR Mol Med"},{"issue":"7","key":"ppat.1013970.ref078","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.bcp.2011.01.001","article-title":"FNC, a novel nucleoside analogue inhibits cell proliferation and tumor growth in a variety of human cancer cells","volume":"81","author":"Q Wang","year":"2011","journal-title":"Biochem 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dehydrogenase as a probe in antiviral drug discovery","volume":"18","author":"V Nair","year":"2007","journal-title":"Antivir Chem Chemother"},{"key":"ppat.1013970.ref086","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.ejmech.2014.11.019","article-title":"New antitumor 6-chloropurine nucleosides inducing apoptosis and G2\/M cell cycle arrest","volume":"90","author":"S Schwarz","year":"2015","journal-title":"Eur J Med Chem"},{"issue":"2","key":"ppat.1013970.ref087","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01522-20","article-title":"Broad-Spectrum Antiviral Activity of 3\u2019-Deoxy-3\u2019-Fluoroadenosine against Emerging Flaviviruses","volume":"65","author":"L Eyer","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"ppat.1013970.ref088","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0966-842X(99)01669-8","article-title":"The causes and consequences of genetic variation in dengue virus","volume":"8","author":"EC Holmes","year":"2000","journal-title":"Trends Microbiol"},{"issue":"6365","key":"ppat.1013970.ref089","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"LC Katzelnick","year":"2017","journal-title":"Science"},{"issue":"1","key":"ppat.1013970.ref090","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4049\/jimmunol.1102124","article-title":"Protection from secondary dengue virus infection in a mouse model reveals the role of serotype cross-reactive B and T cells","volume":"188","author":"S Zompi","year":"2012","journal-title":"J Immunol"},{"issue":"24","key":"ppat.1013970.ref091","doi-asserted-by":"crossref","first-page":"15123","DOI":"10.1128\/JVI.79.24.15123-15130.2005","article-title":"Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence","volume":"79","author":"C Zhang","year":"2005","journal-title":"J Virol"},{"issue":"5","key":"ppat.1013970.ref092","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.celrep.2018.10.006","article-title":"Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization","volume":"25","author":"EN Gallichotte","year":"2018","journal-title":"Cell Rep"},{"key":"ppat.1013970.ref093","doi-asserted-by":"crossref","first-page":"100506","DOI":"10.1016\/j.onehlt.2023.100506","article-title":"The significance of mosquito saliva in arbovirus transmission and pathogenesis in the vertebrate host","volume":"16","author":"I Visser","year":"2023","journal-title":"One Health"},{"issue":"8","key":"ppat.1013970.ref094","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.pt.2017.04.003","article-title":"Mosquito Biting Modulates Skin Response to Virus Infection","volume":"33","author":"M Pingen","year":"2017","journal-title":"Trends Parasitol"},{"issue":"12","key":"ppat.1013970.ref095","doi-asserted-by":"crossref","first-page":"7705","DOI":"10.1074\/jbc.M709563200","article-title":"Structural insights into mechanisms of catalysis and inhibition in Norwalk virus polymerase","volume":"283","author":"DF Zamyatkin","year":"2008","journal-title":"J Biol Chem"},{"issue":"70","key":"ppat.1013970.ref096","doi-asserted-by":"crossref","first-page":"115315","DOI":"10.18632\/oncotarget.23258","article-title":"Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion","volume":"8","author":"K Lee","year":"2017","journal-title":"Oncotarget"},{"issue":"24","key":"ppat.1013970.ref097","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1021\/bi900623r","article-title":"Mechanism of the orotidine 5\u2019-monophosphate decarboxylase-catalyzed reaction: evidence for substrate destabilization","volume":"48","author":"KK Chan","year":"2009","journal-title":"Biochemistry"},{"issue":"2","key":"ppat.1013970.ref098","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1128\/jb.156.2.620-624.1983","article-title":"Purification and characterization of orotidine-5\u2019-phosphate decarboxylase from Escherichia coli K-12","volume":"156","author":"WP Donovan","year":"1983","journal-title":"J Bacteriol"},{"issue":"18","key":"ppat.1013970.ref099","doi-asserted-by":"crossref","first-page":"8402","DOI":"10.1016\/S0021-9258(18)43508-9","article-title":"In vivo synthesis of 6-azauridine 5\u2019-triphosphate and incorporation of 6-azauridine into RNA of germinating wheat embryonic axes","volume":"255","author":"S Rodaway","year":"1980","journal-title":"Journal of Biological Chemistry"},{"key":"ppat.1013970.ref100","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1749-6632.1977.tb21977.x","article-title":"Antiviral action and selectivity of 6-azauridine","volume":"284","author":"B Rada","year":"1977","journal-title":"Ann N Y Acad Sci"},{"issue":"49","key":"ppat.1013970.ref101","doi-asserted-by":"crossref","first-page":"49164","DOI":"10.1074\/jbc.M305041200","article-title":"Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro","volume":"278","author":"G Migliaccio","year":"2003","journal-title":"J Biol Chem"},{"key":"ppat.1013970.ref102","first-page":"1","article-title":"Remdesivir is active in vitro against tick-borne encephalitis virus and selects for resistance mutations in the viral RNA-dependent RNA polymerase","volume":"0","author":"K Nystr\u00f6m","year":"2025","journal-title":"Infect Dis (Auckl)"},{"issue":"1","key":"ppat.1013970.ref103","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":"G Kokic","year":"2021","journal-title":"Nat Commun"},{"issue":"7987","key":"ppat.1013970.ref104","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41586-023-06649-6","article-title":"A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes","volume":"623","author":"T Sanderson","year":"2023","journal-title":"Nature"},{"issue":"34","key":"ppat.1013970.ref105","doi-asserted-by":"crossref","first-page":"35638","DOI":"10.1074\/jbc.M400460200","article-title":"A structural basis for the inhibition of the NS5 dengue virus mRNA 2\u2019-O-methyltransferase domain by ribavirin 5\u2019-triphosphate","volume":"279","author":"D Benarroch","year":"2004","journal-title":"J Biol Chem"},{"key":"ppat.1013970.ref106","doi-asserted-by":"crossref","first-page":"104708","DOI":"10.1016\/j.antiviral.2020.104708","article-title":"Evaluation of sofosbuvir activity and resistance profile against West Nile virus in vitro","volume":"175","author":"F Dragoni","year":"2020","journal-title":"Antiviral Res"},{"issue":"4","key":"ppat.1013970.ref107","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.bbrc.2017.03.068","article-title":"Flaviviridae viruses use a common molecular mechanism to escape nucleoside analogue inhibitors","volume":"492","author":"JJ Vald\u00e9s","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"ppat.1013970.ref108","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.virol.2005.10.030","article-title":"A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection","volume":"346","author":"TC Pierson","year":"2006","journal-title":"Virology"},{"issue":"13","key":"ppat.1013970.ref109","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1093\/nar\/gkae500","article-title":"Motif-VI loop acts as a nucleotide valve in the West Nile Virus NS3 Helicase","volume":"52","author":"P Roy","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"ppat.1013970.ref110","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd4010","article-title":"Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases","volume":"12","author":"LP Jordheim","year":"2013","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"ppat.1013970.ref111","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1128\/AAC.02350-13","article-title":"Metabolism and pharmacokinetics of the anti-hepatitis C virus nucleotide prodrug GS-6620","volume":"58","author":"E Murakami","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"ppat.1013970.ref112","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s10549-011-1477-3","article-title":"Deoxycytidine kinase is overexpressed in poor outcome breast cancer and determines responsiveness to nucleoside analogs","volume":"131","author":"E-J Geutjes","year":"2012","journal-title":"Breast Cancer Res Treat"},{"issue":"1","key":"ppat.1013970.ref113","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/00008571-200301000-00005","article-title":"A functional single-nucleotide polymorphism in the human cytidine deaminase gene contributing to ara-C sensitivity","volume":"13","author":"L Yue","year":"2003","journal-title":"Pharmacogenetics"},{"issue":"16","key":"ppat.1013970.ref114","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1021\/jm100432w","article-title":"Improved syntheses of 5\u2019-S-(2-aminoethyl)-6-N-(4-nitrobenzyl)-5\u2019-thioadenosine (SAENTA), analogues, and fluorescent probe conjugates: analysis of cell-surface human equilibrative nucleoside transporter 1 (hENT1) levels for prediction of the antitumor efficacy of gemcitabine","volume":"53","author":"MJ Robins","year":"2010","journal-title":"J Med Chem"},{"issue":"20","key":"ppat.1013970.ref115","doi-asserted-by":"crossref","first-page":"6956","DOI":"10.1158\/1078-0432.CCR-04-0224","article-title":"The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma","volume":"10","author":"J Spratlin","year":"2004","journal-title":"Clin Cancer Res"},{"issue":"2","key":"ppat.1013970.ref116","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.virusres.2004.11.005","article-title":"Cell entry and export of nucleoside analogues","volume":"107","author":"M Pastor-Anglada","year":"2005","journal-title":"Virus Res"},{"issue":"3","key":"ppat.1013970.ref117","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1124\/dmd.122.000856","article-title":"Cell and Tissue Specific Metabolism of Nucleoside and Nucleotide Drugs: Case Studies and Implications for Precision Medicine","volume":"51","author":"To EE","year":"2023","journal-title":"Drug Metab Dispos"},{"issue":"5","key":"ppat.1013970.ref118","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s13318-015-0267-4","article-title":"Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2\u2019-methylguanosine-5\u2019-monophosphate, in the monkey and formulation optimization for human exposure","volume":"41","author":"X-R Pan-Zhou","year":"2016","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"3","key":"ppat.1013970.ref119","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004682","article-title":"A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication","volume":"11","author":"Y Zhao","year":"2015","journal-title":"PLoS Pathog"},{"issue":"8","key":"ppat.1013970.ref120","article-title":"Potent Allosteric Dengue Virus NS5 Polymerase Inhibitors: Mechanism of Action and Resistance 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