{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:49:40Z","timestamp":1787003380657,"version":"build-2736575974"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Swiss National Science Foundation | nccr \u2013 chemical biology"},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["316030_170799 \/ 1"],"award-info":[{"award-number":["316030_170799 \/ 1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_179256 \/ 1"],"award-info":[{"award-number":["31003A_179256 \/ 1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Data"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and performed robust image analyses and hit filtering. We present the entire set of the screening data including all images, image analyses and data processing pipelines. The data are made available at the Image Data Resource (IDR, idr0081). Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential.<\/jats:p>","DOI":"10.1038\/s41597-020-00604-0","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T06:06:55Z","timestamp":1597212415000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-5099","authenticated-orcid":false,"given":"Fanny","family":"Georgi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2575-1989","authenticated-orcid":false,"given":"Fabien","family":"Kuttler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Murer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vardan","family":"Andriasyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-3517","authenticated-orcid":false,"given":"Robert","family":"Witte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Yakimovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-223X","authenticated-orcid":false,"given":"Gerardo","family":"Turcatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-120X","authenticated-orcid":false,"given":"Urs F.","family":"Greber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"604_CR1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1097\/01.inf.0000165306.95815.68","volume":"24","author":"LR Krilov","year":"2005","unstructured":"Krilov, L. R. Adenovirus infections in the immunocompromised host. Pediatr Infect Dis J 24, 555\u2013556 (2005).","journal-title":"Pediatr Infect Dis J"},{"key":"604_CR2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/cmi.12031","volume":"15","author":"UF Greber","year":"2013","unstructured":"Greber, U. F., Arnberg, N., Wadell, G., Benk\u0151, M. & Kremer, E. J. Adenoviruses - from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting. Cell Microbiol 15, 16\u201323 (2013).","journal-title":"Cell Microbiol"},{"key":"604_CR3","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1056\/NEJMcpc1904045","volume":"381","author":"AR Tunkel","year":"2019","unstructured":"Tunkel, A. R., Baron, E. L., Buch, K. A., Marty, F. M. & Martinez-Lage, M. Case 31-2019: A 45-Year-Old Woman with Headache and Somnolence. N Engl J Med 381, 1459\u20131470 (2019).","journal-title":"N Engl J Med"},{"key":"604_CR4","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1086\/522188","volume":"45","author":"GC Gray","year":"2007","unstructured":"Gray, G. C. et al. Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006. Clin Infect Dis 45, 1120\u20131131 (2007).","journal-title":"Clin Infect Dis"},{"key":"604_CR5","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1086\/522970","volume":"196","author":"D Metzgar","year":"2007","unstructured":"Metzgar, D. et al. Abrupt emergence of diverse species B adenoviruses at US military recruit training centers. J Infect Dis 196, 1465\u20131473 (2007).","journal-title":"J Infect Dis"},{"key":"604_CR6","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1055\/s-0036-1584923","volume":"37","author":"JP Lynch","year":"2016","unstructured":"Lynch, J. P. & Kajon, A. E. Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med 37, 586\u2013602 (2016).","journal-title":"Semin Respir Crit Care Med"},{"key":"604_CR7","doi-asserted-by":"publisher","first-page":"e0194516","DOI":"10.1371\/journal.pone.0194516","volume":"13","author":"E Haque","year":"2018","unstructured":"Haque, E., Banik, U., Monowar, T., Anthony, L. & Adhikary, A. K. Worldwide increased prevalence of human adenovirus type 3 (HAdV-3) respiratory infections is well correlated with heterogeneous hypervariable regions (HVRs) of hexon. PLoS ONE 13, e0194516 (2018).","journal-title":"PLoS ONE"},{"key":"604_CR8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.coviro.2015.03.009","volume":"13","author":"H Jiang","year":"2015","unstructured":"Jiang, H. et al. Oncolytic adenovirus research evolution: from cell-cycle checkpoints to immune checkpoints. Curr Opin Virol 13, 33\u201339 (2015).","journal-title":"Curr Opin Virol"},{"key":"604_CR9","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1001\/jamaoncol.2016.2064","volume":"3","author":"SE Lawler","year":"2017","unstructured":"Lawler, S. E., Speranza, M.-C., Cho, C.-F. & Chiocca, E. A. Oncolytic viruses in cancer treatment: A review. JAMA Oncology 3, 841\u2013849 (2017).","journal-title":"JAMA Oncology"},{"key":"604_CR10","doi-asserted-by":"publisher","first-page":"e3015","DOI":"10.1002\/jgm.3015","volume":"20","author":"SL Ginn","year":"2018","unstructured":"Ginn, S. L., Amaya, A. K., Alexander, I. E., Edelstein, M. & Abedi, M. R. Gene therapy clinical trials worldwide to 2017: An update. J Gene Med 20, e3015 (2018).","journal-title":"J Gene Med"},{"key":"604_CR11","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1080\/14760584.2019.1588113","volume":"18","author":"FJD Mennechet","year":"2019","unstructured":"Mennechet, F. J. D. et al. A review of 65 years of human adenovirus seroprevalence. Expert Rev Vaccines 18, 597\u2013613 (2019).","journal-title":"Expert Rev Vaccines"},{"key":"604_CR12","doi-asserted-by":"publisher","unstructured":"Lion, T. Adenovirus persistence, reactivation, and clinical management. FEBS Lett, https:\/\/doi.org\/10.1002\/1873-3468.13576 (2019).","DOI":"10.1002\/1873-3468.13576"},{"key":"604_CR13","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1002\/1873-3468.13693","volume":"593","author":"AM Ismail","year":"2019","unstructured":"Ismail, A. M. et al. Genomic foundations of evolution and ocular pathogenesis in human adenovirus species D. FEBS Lett 593, 3583\u20133608 (2019).","journal-title":"FEBS Lett"},{"key":"604_CR14","doi-asserted-by":"publisher","unstructured":"Harrach, B., Tarj\u00e1n, Z. L. & Benk\u0151, M. Adenoviruses across the animal kingdom: a walk in the zoo. FEBS Lett, https:\/\/doi.org\/10.1002\/1873-3468.13687 (2019).","DOI":"10.1002\/1873-3468.13687"},{"key":"604_CR15","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1126\/science.1187292","volume":"329","author":"VS Reddy","year":"2010","unstructured":"Reddy, V. S., Natchiar, S. K., Stewart, P. L. & Nemerow, G. R. Crystal structure of human adenovirus at 3.5 A resolution. Science 329, 1071\u20131075 (2010).","journal-title":"Science"},{"key":"604_CR16","doi-asserted-by":"publisher","first-page":"11421","DOI":"10.1074\/jbc.M113.537498","volume":"289","author":"M Benevento","year":"2014","unstructured":"Benevento, M. et al. Adenovirus composition, proteolysis, and disassembly studied by in-depth qualitative and quantitative proteomics. J Biol Chem 289, 11421\u201311430 (2014).","journal-title":"J Biol Chem"},{"key":"604_CR17","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev-virology-092818-015550","volume":"6","author":"UF Greber","year":"2019","unstructured":"Greber, U. F. & Flatt, J. W. Adenovirus entry: from infection to immunity. Annual review of virology 6, 177\u2013197 (2019).","journal-title":"Annual review of virology"},{"key":"604_CR18","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1016\/j.celrep.2019.11.064","volume":"29","author":"M Bauer","year":"2019","unstructured":"Bauer, M. et al. The e3 ubiquitin ligase mind bomb 1 controls adenovirus genome release at the nuclear pore complex. Cell Rep 29, 3785\u20133795.e8 (2019).","journal-title":"Cell Rep"},{"key":"604_CR19","doi-asserted-by":"publisher","first-page":"3802","DOI":"10.1128\/JVI.02568-15","volume":"90","author":"UF Greber","year":"2016","unstructured":"Greber, U. F. Virus and host mechanics support membrane penetration and cell entry. J Virol 90, 3802\u20133805 (2016).","journal-title":"J Virol"},{"key":"604_CR20","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1242\/jcs.203794","volume":"130","author":"I-H Wang","year":"2017","unstructured":"Wang, I.-H., Burckhardt, C. J., Yakimovich, A., Morf, M. K. & Greber, U. F. The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport. J Cell Sci 130, 2185\u20132195 (2017).","journal-title":"J Cell Sci"},{"key":"604_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15844-2","volume":"11","author":"V Prasad","year":"2020","unstructured":"Prasad, V. et al. The UPR sensor IRE1\u03b1 and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections. Nat Commun 11, 1997 (2020).","journal-title":"Nat Commun"},{"key":"604_CR22","doi-asserted-by":"crossref","unstructured":"King, C. R., Zhang, A., Tessier, T. M., Gameiro, S. F. & Mymryk, J. S. Hacking the cell: network intrusion and exploitation by adenovirus E1A. MBio 9, (2018).","DOI":"10.1128\/mBio.00390-18"},{"key":"604_CR23","doi-asserted-by":"publisher","first-page":"e1005415","DOI":"10.1371\/journal.ppat.1005415","volume":"12","author":"Y Zheng","year":"2016","unstructured":"Zheng, Y., Stamminger, T. & Hearing, P. E2f\/rb family proteins mediate interferon induced repression of adenovirus immediate early transcription to promote persistent viral infection. PLoS Pathog 12, e1005415 (2016).","journal-title":"PLoS Pathog"},{"key":"604_CR24","doi-asserted-by":"publisher","first-page":"10123","DOI":"10.1128\/JVI.01102-12","volume":"86","author":"A Yakimovich","year":"2012","unstructured":"Yakimovich, A. et al. Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model. J Virol 86, 10123\u201310137 (2012).","journal-title":"J Virol"},{"key":"604_CR25","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1128\/JVI.70.4.2296-2306.1996","volume":"70","author":"AE Tollefson","year":"1996","unstructured":"Tollefson, A. E. et al. The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. J Virol 70, 2296\u20132306 (1996).","journal-title":"J Virol"},{"key":"604_CR26","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1006\/viro.2002.1772","volume":"305","author":"K Doronin","year":"2003","unstructured":"Doronin, K. et al. Overexpression of the ADP (E3-11.6K) protein increases cell lysis and spread of adenovirus. Virology 305, 378\u2013387 (2003).","journal-title":"Virology"},{"key":"604_CR27","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.antiviral.2006.04.007","volume":"71","author":"L Lenaerts","year":"2006","unstructured":"Lenaerts, L. & Naesens, L. Antiviral therapy for adenovirus infections. Antiviral Res 71, 172\u2013180 (2006).","journal-title":"Antiviral Res"},{"key":"604_CR28","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/femsre\/fuz008","volume":"43","author":"WSM Wold","year":"2019","unstructured":"Wold, W. S. M., Tollefson, A. E., Ying, B., Spencer, J. F. & Toth, K. Drug development against human adenoviruses and its advancement by Syrian hamster models. FEMS Microbiol Rev 43, 380\u2013388 (2019).","journal-title":"FEMS Microbiol Rev"},{"key":"604_CR29","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.c.5052965","author":"F Georgi","year":"2020","unstructured":"Georgi, F. et al. High-content image-based drug screen identifies a clinical compound against cell transmission of adenovirus. figshare https:\/\/doi.org\/10.6084\/m9.figshare.c.5052965 (2020)."},{"key":"604_CR30","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1016\/j.celrep.2017.10.076","volume":"21","author":"C Chauvin","year":"2017","unstructured":"Chauvin, C. et al. High-Throughput Drug Screening Identifies Pazopanib and Clofilium Tosylate as Promising Treatments for Malignant Rhabdoid Tumors. Cell Rep 21, 1737\u20131745 (2017).","journal-title":"Cell Rep"},{"key":"604_CR31","doi-asserted-by":"crossref","unstructured":"Wall, G. et al. Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development. Antimicrob Agents Chemother 62 (2018).","DOI":"10.1128\/AAC.01084-18"},{"key":"604_CR32","doi-asserted-by":"publisher","first-page":"e0138760","DOI":"10.1371\/journal.pone.0138760","volume":"10","author":"A Yakimovich","year":"2015","unstructured":"Yakimovich, A. et al. Plaque2.0-A High-Throughput Analysis Framework to Score Virus-Cell Transmission and Clonal Cell Expansion. PLoS ONE 10, e0138760 (2015).","journal-title":"PLoS ONE"},{"key":"604_CR33","doi-asserted-by":"publisher","DOI":"10.17867\/10000136","author":"F Georgi","year":"2020","unstructured":"Georgi, F. et al. High-content image-based drug screen identifies a clinical compound against cell transmission of adenovirus. University of Dundee https:\/\/doi.org\/10.17867\/10000136 (2020)."},{"key":"604_CR34","doi-asserted-by":"publisher","unstructured":"Georgi, F. et al. The FDA-approved drug Nelfinavir inhibits lytic cell-free, but not cell-associated non-lytic transmission of human adenovirus. Antimicrob Agents Chemother, https:\/\/doi.org\/10.1128\/AAC.01002-20\u00a0(2020).","DOI":"10.1128\/AAC.01002-20"},{"key":"604_CR35","unstructured":"Georgi, F. et al. Mutant Human adenovirus 2 isolate HAdV-C2-dE3B-CMV-GFP, complete sequence. GenBank https:\/\/identifiers.org\/ncbi\/insdc:MT277585.1 (2020)."},{"key":"604_CR36","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\u2013486 (1993).","journal-title":"Cell"},{"key":"604_CR37","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.vascn.2013.09.003","volume":"69","author":"M Boncler","year":"2014","unstructured":"Boncler, M., R\u00f3\u017calski, M., Krajewska, U., Pods\u0119dek, A. & Watala, C. Comparison of PrestoBlue and MTT assays of cellular viability in the assessment of anti-proliferative effects of plant extracts on human endothelial cells. J Pharmacol Toxicol Methods 69, 9\u201316 (2014).","journal-title":"J Pharmacol Toxicol Methods"},{"key":"604_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vascn.2014.11.003","volume":"71","author":"M Xu","year":"2015","unstructured":"Xu, M., McCanna, D. J. & Sivak, J. G. Use of the viability reagent PrestoBlue in comparison with alamarBlue and MTT to assess the viability of human corneal epithelial cells. J Pharmacol Toxicol Methods 71, 1\u20137 (2015).","journal-title":"J Pharmacol Toxicol Methods"},{"key":"604_CR39","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. (R Foundation for Statistical Computing, 2018)."},{"key":"604_CR40","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1145\/1656274.1656280","volume":"11","author":"MR Berthold","year":"2009","unstructured":"Berthold, M. R. et al. KNIME - the Konstanz information miner. ACM SIGKDD Explorations Newsletter 11, 26 (2009).","journal-title":"ACM SIGKDD Explorations Newsletter"}],"container-title":["Scientific Data"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41597-020-00604-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41597-020-00604-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41597-020-00604-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:26:29Z","timestamp":1670286389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41597-020-00604-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,12]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["604"],"URL":"https:\/\/doi.org\/10.1038\/s41597-020-00604-0","relation":{"references":[{"id-type":"doi","id":"10.6084\/m9.figshare.c.5052965","asserted-by":"subject"},{"id-type":"doi","id":"10.17867\/10000136","asserted-by":"subject"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.24.006346","asserted-by":"object"}]},"ISSN":["2052-4463"],"issn-type":[{"value":"2052-4463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,12]]},"assertion":[{"value":"18 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2020","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":"265"}}