{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:35:36Z","timestamp":1789824936848,"version":"4.0.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009042","name":"Universidad de Sevilla","doi-asserted-by":"publisher","award":["USE-16591-P"],"award-info":[{"award-number":["USE-16591-P"]}],"id":[{"id":"10.13039\/100009042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.<\/jats:p>","DOI":"10.1038\/s41598-018-37290-3","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T15:17:33Z","timestamp":1546528653000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections"],"prefix":"10.1038","volume":"9","author":[{"given":"Jos\u00e9 A.","family":"Marrugal-Lorenzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Serna-Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Berastegui-Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer\u00f3nimo","family":"Pach\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-1979","authenticated-orcid":false,"given":"Javier","family":"S\u00e1nchez-C\u00e9spedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,9]]},"reference":[{"key":"37290_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/srep01812","volume":"3","author":"CM Robinson","year":"2013","unstructured":"Robinson, C. M. et al. Molecular evolution of human adenoviruses. Sci Rep 3, 1812 (2013).","journal-title":"Sci Rep"},{"key":"37290_CR2","doi-asserted-by":"publisher","first-page":"e401","DOI":"10.1016\/j.ijid.2011.02.006","volume":"15","author":"V Wiegering","year":"2011","unstructured":"Wiegering, V. et al. Gastroenteritis in childhood: a retrospective study of 650 hospitalized pediatric patients. Int J Infect Dis 15, e401\u20137 (2011).","journal-title":"Int J Infect Dis"},{"key":"37290_CR3","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1002\/jmv.21136","volume":"80","author":"S Wong","year":"2008","unstructured":"Wong, S., Pabbaraju, K., Pang, X. L., Lee, B. E. & Fox, J. D. Detection of a broad range of human adenoviruses in respiratory tract samples using a sensitive multiplex real-time PCR assay. J Med Virol 80, 856\u201365 (2008).","journal-title":"J Med Virol"},{"key":"37290_CR4","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1128\/CMR.00052-07","volume":"21","author":"M Echavarria","year":"2008","unstructured":"Echavarria, M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 21, 704\u201315 (2008).","journal-title":"Clin Microbiol Rev"},{"key":"37290_CR5","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1128\/CMR.00116-13","volume":"27","author":"T Lion","year":"2014","unstructured":"Lion, T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev 27, 441\u201362 (2014).","journal-title":"Clin Microbiol Rev"},{"key":"37290_CR6","doi-asserted-by":"publisher","first-page":"e0151199","DOI":"10.1371\/journal.pone.0151199","volume":"11","author":"D Tan","year":"2016","unstructured":"Tan, D. et al. Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series. PLoS One 11, e0151199 (2016).","journal-title":"PLoS One"},{"key":"37290_CR7","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3201\/eid2204.151403","volume":"22","author":"AE Kajon","year":"2016","unstructured":"Kajon, A. E. & Ison, M. G. Severe Infections with Human Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014. Emerg Infect Dis 22, 730\u20133 (2016).","journal-title":"Emerg Infect Dis"},{"key":"37290_CR8","doi-asserted-by":"publisher","first-page":"e0171687","DOI":"10.1371\/journal.pone.0171687","volume":"12","author":"S Jonnalagadda","year":"2017","unstructured":"Jonnalagadda, S. et al. Etiology of severe pneumonia in Ecuadorian children. PLoS One 12, e0171687 (2017).","journal-title":"PLoS One"},{"key":"37290_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-016-2370-2","volume":"10","author":"BW Yoon","year":"2017","unstructured":"Yoon, B. W., Song, Y. G. & Lee, S. H. Severe community-acquired adenovirus pneumonia treated with oral ribavirin: a case report. BMC Res Notes 10, 47 (2017).","journal-title":"BMC Res Notes"},{"key":"37290_CR10","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1016\/j.drudis.2015.07.007","volume":"20","author":"P Martinez-Aguado","year":"2015","unstructured":"Martinez-Aguado, P., Serna-Gallego, A., Marrugal-Lorenzo, J. A., Gomez-Marin, I. & Sanchez-Cespedes, J. Antiadenovirus drug discovery: potential targets and evaluation methodologies. Drug Discov Today 20, 1235\u201342 (2015).","journal-title":"Drug Discov Today"},{"key":"37290_CR11","unstructured":"Soo, V. W. et al. Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections. Curr Top Med Chem (2016)."},{"key":"37290_CR12","doi-asserted-by":"crossref","unstructured":"Cheng, F., Murray, J. L. & Rubin, D. H. Drug Repurposing: New Treatments for Zika Virus Infection? Trends Mol Med (2016).","DOI":"10.1016\/j.molmed.2016.09.006"},{"key":"37290_CR13","doi-asserted-by":"crossref","unstructured":"Pietschmann, T. Clinically approved ion channel inhibitors close gates for hepatitis C virus -and open doors for drug repurposing in viral infectious diseases. J Virol (2016).","DOI":"10.1128\/JVI.01914-16"},{"key":"37290_CR14","doi-asserted-by":"publisher","first-page":"e1002976","DOI":"10.1371\/journal.ppat.1002976","volume":"8","author":"A Jurgeit","year":"2012","unstructured":"Jurgeit, A. et al. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects. PLoS Pathog 8, e1002976 (2012).","journal-title":"PLoS Pathog"},{"key":"37290_CR15","doi-asserted-by":"publisher","first-page":"e78425","DOI":"10.1371\/journal.pone.0078425","volume":"8","author":"J Fang","year":"2013","unstructured":"Fang, J. et al. Identification of three antiviral inhibitors against Japanese encephalitis virus from library of pharmacologically active compounds 1280. PLoS One 8, e78425 (2013).","journal-title":"PLoS One"},{"key":"37290_CR16","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1128\/AAC.48.7.2693-2696.2004","volume":"48","author":"CJ Wu","year":"2004","unstructured":"Wu, C. J. et al. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob Agents Chemother 48, 2693\u20136 (2004).","journal-title":"Antimicrob Agents Chemother"},{"key":"37290_CR17","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nm.4184","volume":"22","author":"M Xu","year":"2016","unstructured":"Xu, M. et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med 22, 1101\u20131107 (2016).","journal-title":"Nat Med"},{"key":"37290_CR18","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/0092-8674(93)90382-Z","volume":"75","author":"UF Greber","year":"1993","unstructured":"Greber, U. F., Willetts, M., Webster, P. & Helenius, A. Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75, 477\u201386 (1993).","journal-title":"Cell"},{"key":"37290_CR19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.antiviral.2014.05.010","volume":"108","author":"J Sanchez-Cespedes","year":"2014","unstructured":"Sanchez-Cespedes, J., Moyer, C. L., Whitby, L. R., Boger, D. L. & Nemerow, G. R. Inhibition of adenovirus replication by a trisubstituted piperazin-2-one derivative. Antiviral Res 108, 65\u201373 (2014).","journal-title":"Antiviral Res"},{"key":"37290_CR20","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1128\/JVI.79.4.1992-2000.2005","volume":"79","author":"CM Wiethoff","year":"2005","unstructured":"Wiethoff, C. M., Wodrich, H., Gerace, L. & Nemerow, G. R. Adenovirus protein VI mediates membrane disruption following capsid disassembly. J Virol 79, 1992\u20132000 (2005).","journal-title":"J Virol"},{"key":"37290_CR21","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.chom.2011.08.010","volume":"10","author":"S Strunze","year":"2011","unstructured":"Strunze, S. et al. Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection. Cell Host Microbe 10, 210\u201323 (2011).","journal-title":"Cell Host Microbe"},{"key":"37290_CR22","doi-asserted-by":"publisher","first-page":"e1002549","DOI":"10.1371\/journal.ppat.1002549","volume":"8","author":"S Schreiner","year":"2012","unstructured":"Schreiner, S. et al. Transcriptional activation of the adenoviral genome is mediated by capsid protein VI. PLoS Pathog 8, e1002549 (2012).","journal-title":"PLoS Pathog"},{"key":"37290_CR23","unstructured":"Horwitz, M.S. Adenoviridae and their replication. In Fields, B. N., Knipe, D. M., Chanock, R. M., et al. (ed. virology, F.) 771\u2013813 (Raven Press, New York, NY, 1991)."},{"key":"37290_CR24","doi-asserted-by":"publisher","first-page":"5476","DOI":"10.1182\/blood-2010-04-259291","volume":"116","author":"CA Lindemans","year":"2010","unstructured":"Lindemans, C. A., Leen, A. M. & Boelens, J. J. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood 116, 5476\u201385 (2010).","journal-title":"Blood"},{"key":"37290_CR25","doi-asserted-by":"publisher","first-page":"5432","DOI":"10.1021\/acs.jmedchem.6b00300","volume":"59","author":"J Sanchez-Cespedes","year":"2016","unstructured":"Sanchez-Cespedes, J. et al. New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships. J Med Chem 59, 5432\u201348 (2016).","journal-title":"J Med Chem"},{"key":"37290_CR26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","volume":"22","author":"TC Chou","year":"1984","unstructured":"Chou, T. C. & Talalay, P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22, 27\u201355 (1984).","journal-title":"Adv Enzyme Regul"},{"key":"37290_CR27","doi-asserted-by":"publisher","first-page":"e0173303","DOI":"10.1371\/journal.pone.0173303","volume":"12","author":"H Matthews","year":"2017","unstructured":"Matthews, H., Deakin, J., Rajab, M., Idris-Usman, M. & Nirmalan, N. J. Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations. PLoS One 12, e0173303 (2017).","journal-title":"PLoS One"},{"key":"37290_CR28","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.2174\/138161211798194521","volume":"17","author":"M Kratky","year":"2011","unstructured":"Kratky, M. & Vinsova, J. Salicylanilide ester prodrugs as potential antimicrobial agents\u2013a review. Curr Pharm Des 17, 3494\u2013505 (2011).","journal-title":"Curr Pharm Des"},{"key":"37290_CR29","doi-asserted-by":"publisher","first-page":"12367","DOI":"10.1128\/JVI.01833-13","volume":"87","author":"M Suomalainen","year":"2013","unstructured":"Suomalainen, M. et al. A direct and versatile assay measuring membrane penetration of adenovirus in single cells. J Virol 87, 12367\u201379 (2013).","journal-title":"J Virol"},{"key":"37290_CR30","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1086\/498151","volume":"41","author":"WJ Muller","year":"2005","unstructured":"Muller, W. J. et al. Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients. Clin Infect Dis 41, 1812\u20136 (2005).","journal-title":"Clin Infect Dis"},{"key":"37290_CR31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1177\/135965350501000204","volume":"10","author":"F Morfin","year":"2005","unstructured":"Morfin, F. et al. In vitro susceptibility of adenovirus to antiviral drugs is species-dependent. Antivir Ther 10, 225\u20139 (2005).","journal-title":"Antivir Ther"},{"key":"37290_CR32","unstructured":"Pettersson, U. & Roberts, R.J. Adenovirus gene expression and replication: a historical review. In DNA tumor viruses: control of gene expression and replication. 37\u201357 (Cold Spring HarborLaboratory, Cold Spring Harbor, N.Y., 1986)."},{"key":"37290_CR33","doi-asserted-by":"publisher","first-page":"e0004584","DOI":"10.1371\/journal.pntd.0004584","volume":"10","author":"M De Rycker","year":"2016","unstructured":"De Rycker, M. et al. Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade. PLoS Negl Trop Dis 10, e0004584 (2016).","journal-title":"PLoS Negl Trop Dis"},{"key":"37290_CR34","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1089\/adt.2015.0003.drrr","volume":"13","author":"O Perwitasari","year":"2015","unstructured":"Perwitasari, O., Yan, X., O\u2019Donnell, J., Johnson, S. & Tripp, R. A. Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication. Assay Drug Dev Technol 13, 638\u201349 (2015).","journal-title":"Assay Drug Dev Technol"},{"key":"37290_CR35","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.virusres.2015.05.025","volume":"209","author":"C Martinez-Romero","year":"2015","unstructured":"Martinez-Romero, C. & Garcia-Sastre, A. Against the clock towards new Ebola virus therapies. Virus Res 209, 4\u201310 (2015).","journal-title":"Virus Res"},{"key":"37290_CR36","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/448645a","volume":"448","author":"CR Chong","year":"2007","unstructured":"Chong, C. R. & Sullivan, D. J. Jr. New uses for old drugs. Nature 448, 645\u20136 (2007).","journal-title":"Nature"},{"key":"37290_CR37","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.bbrc.2016.10.064","volume":"480","author":"Y Liu","year":"2016","unstructured":"Liu, Y., Fang, S., Sun, Q. & Liu, B. Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress. Biochem Biophys Res Commun 480, 415\u2013421 (2016).","journal-title":"Biochem Biophys Res Commun"},{"key":"37290_CR38","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jss.2016.03.051","volume":"203","author":"MB Monin","year":"2016","unstructured":"Monin, M. B. et al. The anthelmintic niclosamide inhibits colorectal cancer cell lines via modulation of the canonical and noncanonical Wnt signaling pathway. J Surg Res 203, 193\u2013205 (2016).","journal-title":"J Surg Res"},{"key":"37290_CR39","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1021\/ml3003082","volume":"4","author":"H Chen","year":"2013","unstructured":"Chen, H. et al. Discovery of O-Alkylamino Tethered Niclosamide Derivatives as Potent and Orally Bioavailable Anticancer Agents. ACS Med Chem Lett 4, 180\u2013185 (2013).","journal-title":"ACS Med Chem Lett"},{"key":"37290_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2011.38","volume":"1","author":"FL Khanim","year":"2011","unstructured":"Khanim, F. L. et al. Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production. Blood Cancer J 1, e39 (2011).","journal-title":"Blood Cancer J"},{"key":"37290_CR41","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.exppara.2007.12.001","volume":"118","author":"K Merschjohann","year":"2008","unstructured":"Merschjohann, K. & Steverding, D. In vitro trypanocidal activity of the anti-helminthic drug niclosamide. Exp Parasitol 118, 637\u201340 (2008).","journal-title":"Exp Parasitol"},{"key":"37290_CR42","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/0163-7258(82)90064-X","volume":"19","author":"P Andrews","year":"1982","unstructured":"Andrews, P., Thyssen, J. & Lorke, D. The biology and toxicology of molluscicides, Bayluscide. Pharmacol Ther 19, 245\u201395 (1982).","journal-title":"Pharmacol Ther"},{"key":"37290_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/srep33642","volume":"6","author":"M Gooyit","year":"2016","unstructured":"Gooyit, M. & Janda, K. D. Reprofiled anthelmintics abate hypervirulent stationary-phase Clostridium difficile. Sci Rep 6, 33642 (2016).","journal-title":"Sci Rep"},{"key":"37290_CR44","first-page":"316","volume":"78","author":"C Gokbulut","year":"2014","unstructured":"Gokbulut, C., Yalinkilinc, H. S., Aksit, D. & Veneziano, V. Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration. Can J Vet Res 78, 316\u201320 (2014).","journal-title":"Can J Vet Res"},{"key":"37290_CR45","first-page":"4","volume":"3","author":"S Pal","year":"2004","unstructured":"Pal, S., Debnath, S. C., Das, S. K., Chakraborty, A. K. & Mandal, T. K. The Pharmacokinetics of Rafoxanide following Single Dose Intravenous and Oral Administration in Goats. Iranian journal of pharmacology & therapeutics 3, 4 (2004).","journal-title":"Iranian journal of pharmacology & therapeutics"},{"key":"37290_CR46","unstructured":"EMEA. Oxyclozanide (Extrapolation to all ruminants): Summary report (3) - Committee for Veterinary Medicinal Products. (2004)."},{"key":"37290_CR47","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1128\/JVI.02471-09","volume":"84","author":"EK Nguyen","year":"2010","unstructured":"Nguyen, E. K., Nemerow, G. R. & Smith, J. G. Direct evidence from single-cell analysis that human {alpha}-defensins block adenovirus uncoating to neutralize infection. J Virol 84, 4041\u20139 (2010).","journal-title":"J Virol"},{"key":"37290_CR48","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/sj.mt.6300048","volume":"15","author":"RR Nepomuceno","year":"2007","unstructured":"Nepomuceno, R. R., Pache, L. & Nemerow, G. R. Enhancement of gene transfer to human myeloid cells by adenovirus-fiber complexes. Mol Ther 15, 571\u20138 (2007).","journal-title":"Mol Ther"},{"key":"37290_CR49","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S0166-3542(02)00077-3","volume":"55","author":"HY Cheng","year":"2002","unstructured":"Cheng, H. Y., Lin, C. C. & Lin, T. C. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral Res 55, 447\u201355 (2002).","journal-title":"Antiviral Res"},{"key":"37290_CR50","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9, 671\u20135 (2012).","journal-title":"Nat Methods"},{"key":"37290_CR51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.antiviral.2018.09.011","volume":"159","author":"JA Marrugal-Lorenzo","year":"2018","unstructured":"Marrugal-Lorenzo, J. A. et al. Inhibition of adenovirus infection by mifepristone. Antiviral Res 159, 77\u201383 (2018).","journal-title":"Antiviral Res"},{"key":"37290_CR52","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.virol.2003.11.028","volume":"320","author":"AA Rivera","year":"2004","unstructured":"Rivera, A. A. et al. Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo. Virology 320, 121\u201334 (2004).","journal-title":"Virology"},{"key":"37290_CR53","first-page":"4","volume":"27","author":"LV Reed","year":"1938","unstructured":"Reed, L. V. & Muench, H. A simple method of stimating fifty percent endpoints. American Journal of Hygiene 27, 4 (1938).","journal-title":"American Journal of Hygiene"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37290-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37290-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37290-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T04:39:40Z","timestamp":1671251980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37290-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,9]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["37290"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-37290-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,9]]},"assertion":[{"value":"4 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"17"}}