{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:51:12Z","timestamp":1791193872509,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T00:00:00Z","timestamp":1461628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100009888","name":"Tuscany Region","doi-asserted-by":"crossref","award":["DD3242\/2009 Bando Salute 2009"],"award-info":[{"award-number":["DD3242\/2009 Bando Salute 2009"]}],"id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PRIN 2010","award":["2010W2KM5L"],"award-info":[{"award-number":["2010W2KM5L"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["SAF2013-46077-R"],"award-info":[{"award-number":["SAF2013-46077-R"]}]},{"name":"MINECO","award":["BFU2012-31569"],"award-info":[{"award-number":["BFU2012-31569"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,5,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Human DEAD-box polypeptide 3 (DDX3) is an ATPase\/RNA helicase involved in the replication of many viral pathogens. We reported herein the first inhibitor, to our knowledge, of the helicase binding site of DDX3 endowed with a broad spectrum antiviral activity [HIV-1 WT, HIV drug-resistant strains, Hepatitis C virus (HCV), Dengue virus (DENV), and West Nile virus (WNV)]. The good toxicity profile suggests that the DDX3 activity, although essential for viruses, could be dispensable to the cells, validating DDX3 as a pharmaceutical target. Our results clearly showed that DDX3 inhibitors could be exploited to treat HIV\/HCV coinfections, emerging infectious diseases (such as DENV and WNV), and HIV-1 patients carrying drug-resistant strains. Each of these three medical conditions currently represents a major challenge for clinical treatment.<\/jats:p>","DOI":"10.1073\/pnas.1522987113","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:06:15Z","timestamp":1461715575000},"page":"5388-5393","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":107,"title":["Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents"],"prefix":"10.1073","volume":"113","author":[{"given":"Annalaura","family":"Brai","sequence":"first","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 degli Studi di Siena, I-53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Fazi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 degli Studi di Siena, I-53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tintori","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 degli Studi di Siena, I-53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Zamperini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 degli Studi di Siena, I-53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bugli","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egidio","family":"Stigliano","sequence":"additional","affiliation":[{"name":"Institute of Pathological Anatomy, University Hospital A. Gemelli, Catholic University of Sacred Heart, 00168 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Est\u00e9","sequence":"additional","affiliation":[{"name":"AIDS Research Institute, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Badia","sequence":"additional","affiliation":[{"name":"AIDS Research Institute, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Franco","sequence":"additional","affiliation":[{"name":"AIDS Research Institute, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6681-4950","authenticated-orcid":false,"given":"Miguel A.","family":"Martinez","sequence":"additional","affiliation":[{"name":"AIDS Research Institute, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier P.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomedica Barcelona, 08003 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Meyerhans","sequence":"additional","affiliation":[{"name":"Infection Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomedica Barcelona, 08003 Barcelona, Spain;"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats, 08010 Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Saladini","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche, Universit\u00e0 degli Studi di Siena, 53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Zazzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Mediche, Universit\u00e0 degli Studi di Siena, 53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Garbelli","sequence":"additional","affiliation":[{"name":"Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (IGM-CNR), 27100 Pavia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-1552","authenticated-orcid":false,"given":"Giovanni","family":"Maga","sequence":"additional","affiliation":[{"name":"Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (IGM-CNR), 27100 Pavia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Botta","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia, Universit\u00e0 degli Studi di Siena, I-53100 Siena, Italy;"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122;"},{"name":"Lead Discovery Siena S.r.l., Castelnuovo Berardenga, 53019 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,4,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.11.006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa3778"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4721-4732.2005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S30946"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.15.8181-8186.2003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12064027"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906413106"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13910"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/655397"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2323"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.139"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4NP00085D"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.008"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.029"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9659"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15751"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.2841-2853.1999"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01517-07"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.11.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.12.011"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.09.041"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.143"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.09.048"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.052670-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00432-12"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0390679"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.06.005"},{"key":"e_1_3_3_28_2","first-page":"183","volume-title":"Topics in Medicinal Chemistry","author":"D\u00fcrr R","year":"2014","unstructured":"R D\u00fcrr, , Targeting cellular cofactors in HIV therapy. Topics in Medicinal Chemistry, eds WE Diederich, H Steuber (Springer, Heidelberg), pp. 183\u2013222 (2014)."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800332m"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.12.121"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986711796391688"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm8008844"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep09982"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404368"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.07.001"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.12.135"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5b00419"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10465"},{"key":"e_1_3_3_39_2","volume-title":"Virtual Screening in Drug Discovery","author":"Cole JC","year":"2005","unstructured":"JC Cole, JWM Nissink, R Taylor, Protein-ligand docking and virtual screening with GOLD. Virtual Screening in Drug Discovery, eds B Shoichet, J Alvarez (Taylor & Francis CRC Press, Boca Raton, FL, 2005)."},{"key":"e_1_3_3_40_2","volume-title":"PyMOL Molecular Graphics System, Version 0.99","author":"PyMOL","year":"2011","unstructured":"; PyMOL PyMOL Molecular Graphics System, Version 0.99 (Schr\u00f6dinger, LLC, New York, NY, 2011)."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.517"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm001020e"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705710100600309"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602538608998295"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1522987113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1522987113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:51:56Z","timestamp":1649814716000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1522987113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,26]]},"references-count":44,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2016,5,10]]}},"alternative-id":["10.1073\/pnas.1522987113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1522987113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,26]]},"assertion":[{"value":"2016-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}