{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:03:41Z","timestamp":1784819021268,"version":"3.55.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2013,10,15]],"date-time":"2013-10-15T00:00:00Z","timestamp":1381795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rotaviruses, nonenveloped viruses presenting a distinctive triple-layered particle architecture enclosing a segmented double-stranded RNA genome, exhibit a unique morphogenetic pathway requiring the formation of cytoplasmic inclusion bodies called viroplasms in a process involving the nonstructural viral proteins NSP5 and NSP2. In these structures the concerted packaging and replication of the 11 positive-polarity single-stranded RNAs take place to generate the viral double-stranded RNA (dsRNA) genomic segments. Rotavirus infection is a leading cause of gastroenteritis-associated severe morbidity and mortality in young children, but no effective antiviral therapy exists. Herein we investigate the antirotaviral activity of the thiazolide anti-infective nitazoxanide and reveal a novel mechanism by which thiazolides act against rotaviruses. Nitazoxanide and its active circulating metabolite, tizoxanide, inhibit simian A\/SA11-G3P[2] and human Wa-G1P[8] rotavirus replication in different types of cells with 50% effective concentrations (EC\n            <jats:sub>50<\/jats:sub>\n            s) ranging from 0.3 to 2 \u03bcg\/ml and 50% cytotoxic concentrations (CC\n            <jats:sub>50<\/jats:sub>\n            s) higher than 50 \u03bcg\/ml. Thiazolides do not affect virus infectivity, binding, or entry into target cells and do not cause a general inhibition of viral protein expression, whereas they reduce the size and alter the architecture of viroplasms, decreasing rotavirus dsRNA formation. As revealed by protein\/protein interaction analysis, confocal immunofluorescence microscopy, and viroplasm-like structure formation analysis, thiazolides act by hindering the interaction between the nonstructural proteins NSP5 and NSP2. Altogether the results indicate that thiazolides inhibit rotavirus replication by interfering with viral morphogenesis and may represent a novel class of antiviral drugs effective against rotavirus gastroenteritis.\n          <\/jats:p>","DOI":"10.1128\/jvi.01213-13","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T06:15:37Z","timestamp":1375942537000},"page":"11096-11106","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["Thiazolides, a New Class of Antiviral Agents Effective against Rotavirus Infection, Target Viral Morphogenesis, Inhibiting Viroplasm Formation"],"prefix":"10.1128","volume":"87","author":[{"given":"Simone","family":"La Frazia","sequence":"first","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ciucci","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Arnoldi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Coira","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Gianferretti","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Angelini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Belardo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar R.","family":"Burrone","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Romark Laboratories, LC, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gabriella","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2673"},{"key":"e_1_3_2_3_2","first-page":"1917","volume-title":"Fields virology","author":"Estes MK","year":"2007","unstructured":"EstesMKKapikianZA. 2007. Rotaviruses, p 1917\u20131974. In KnipeDMHowleyPMGriffinDELambRAMartinMARoizmanBStrausSE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00326-X"},{"key":"e_1_3_2_5_2","first-page":"26","article-title":"Rotavirus disease and its prevention","volume":"21","author":"Widdowson MA","year":"2005","unstructured":"WiddowsonMABreseeJSGentschJRGlassRI. 2005. Rotavirus disease and its prevention. Curr. Opin. Gastroenterol. 21:26\u201331.","journal-title":"Curr. Opin. Gastroenterol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70253-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68852-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03128.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19611-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4282"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-11-2679"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-2-333"},{"key":"e_1_3_2_13_2","volume-title":"Molecular cloning, a laboratory manual","author":"Sambrook J","year":"1989","unstructured":"SambrookJFritschEFManiatisT. 1989. Molecular cloning, a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.","edition":"2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/517475"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.029470"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20111236"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01494-06"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1385\/1-59259-078-0:33","volume-title":"Rotaviruses: methods and protocols","author":"Patton J","year":"2000","unstructured":"PattonJChizhikovVTaraporewalaZChenDY. 2000. Virus replication, p 33\u201336In GrayJDesselbergerU (ed), Rotaviruses: methods and protocols. Humana Press, Totowa, NJ."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-9-2059"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.082693"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900867"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808480105"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0168-7069(03)09020-7","volume-title":"Viral gastroenteritis","author":"Offit PA","year":"2003","unstructured":"OffitPAClarkHFWardRL. 2003. Current state of development of human rotavirus vaccines, p 345\u2013356. In DesselbergerUGrayJ (ed), Viral gastroenteritis. Elsevier Science BV, Amsterdam, Netherlands."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(84)90069-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80598-0"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.14.7763-7774.2004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2010.12.002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02308-08"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2.1.43"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9010719"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.11.037"},{"key":"e_1_3_2_32_2","first-page":"46","volume-title":"A randomized double-blind, placebo (PCB) controlled study of nitazoxanide (NTZ) in adults and adolescents with acute uncomplicated influenza, abstr LB-35","author":"Rossignol JF","year":"2011","unstructured":"RossignolJFSamudralaSHoppersMHaffizullaJResnickHHartmanAComhaireSCarrionMBardinM. 2011. A randomized double-blind, placebo (PCB) controlled study of nitazoxanide (NTZ) in adults and adolescents with acute uncomplicated influenza, abstr LB-35, p 46. Abstr. 49th Annu. Meet. Infect. Dis. Soc. Am., Boston, MA."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01159-06"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002691"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.08.005"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.07.056"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2008.09.014"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.5414\/CPP38387"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01213-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01213-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T13:56:09Z","timestamp":1646488569000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01213-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,15]]},"references-count":37,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2013,10,15]]}},"alternative-id":["10.1128\/JVI.01213-13"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01213-13","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,15]]},"assertion":[{"value":"2013-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}