{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:53:15Z","timestamp":1792619595989,"version":"4.5.0"},"reference-count":44,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"crossref","award":["UBACyT 20020130100584"],"award-info":[{"award-number":["UBACyT 20020130100584"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"crossref","award":["PICT 2018\u201300733"],"award-info":[{"award-number":["PICT 2018\u201300733"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"crossref","award":["PIP 20120100538"],"award-info":[{"award-number":["PIP 20120100538"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The emergence and re-emergence of viruses has highlighted the need to develop new broad-spectrum antivirals to mitigate human infections. Pursuing our search for new bioactive plant-derived\n          molecules, we study several diterpene derivatives synthesized from jatropholones A and B and carnosic acid isolated from Jatropha isabellei and Rosmarinus officinalis,\n          respectively. Here, we investigate the antiviral effect of the diterpenes against human adenovirus (HAdV-5) that causes several infections for which there is no approved antiviral therapy\n          yet. Ten compounds are evaluated and none of them present cytotoxicity in A549 cells. Only compounds 2, 5 and 9 inhibit HAdV-5 replication in a concentration-dependent manner, without\n          virucidal activity, whereas the antiviral action takes place after virus internalization. The expression of viral proteins E1A and Hexon is strongly inhibited by compounds 2 and 5 and, in a\n          lesser degree, by compound 9. Since compounds 2, 5 and 9 prevent ERK activation, they might exert their antiviral action by interfering in the host cell functions required for virus\n          replication. Besides, the compounds have an anti-inflammatory profile since they significantly inhibit the levels of IL-6 and IL-8 produced by THP-1 cells infected with HAdV-5 or with an\n          adenoviral vector. In conclusion, diterpenes 2, 5 and 9 not only exert antiviral activity against adenovirus but also are able to restrain pro-inflammatory cytokines induced by the\n          virus.<\/jats:p>","DOI":"10.1055\/a-2058-3635","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T09:31:48Z","timestamp":1680600708000},"page":"1001-1009","source":"Crossref","is-referenced-by-count":6,"title":["Antiviral Effect of Natural and Semisynthetic Diterpenoids against Adenovirus Infection in vitro"],"prefix":"10.1055","volume":"89","author":[{"given":"Juan Esteban","family":"Bidart","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Instituto de Virolog\u00eda e Innovaciones Tecnol\u00f3gicas-IVIT, CICVyA, INTA-CONICET, Hurlingham, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano Walter","family":"Pertino","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica de Productos Naturales, Instituto de Qu\u00edmica de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Schmeda-Hirschmann","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica de Productos Naturales, Instituto de Qu\u00edmica de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Edith","family":"Alch\u00e9","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-7461","authenticated-orcid":false,"given":"Erina","family":"Petrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"ref1","first-page":"1","article-title":"Adenovirus","volume":"4","author":"M G Ison","year":"2016","journal-title":"Microbiol Spectr"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1128\/CMR.00116-13","article-title":"Adenovirus infections in immunocompetent and immunocompromised patients","volume":"27","author":"T Lion","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.bbmt.2013.11.009","article-title":"Patient, virus, and treatment-related risk factors in pediatric adenovirus infection after stem cell transplantation: Results of a routine monitoring program","volume":"20","author":"M Mynarek","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1086\/341770","article-title":"High levels of adenovirus DNA in serum correlate with fatal outcome of adenovirus infection in children after allogeneic stem\u2010cell transplantation","volume":"35","author":"M W Schilham","year":"2002","journal-title":"Clin Infect Dis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/leu.2010.4","article-title":"Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation","volume":"24","author":"T Lion","year":"2010","journal-title":"Leukemia"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1517\/14656566.2015.1083975","article-title":"New drug on the horizon for treating adenovirus","volume":"16","author":"W SM Wold","year":"2015","journal-title":"Expert Opin Pharmacother"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JVI.01623-16","article-title":"Suppression of adenovirus replication by cardiotonic steroids","volume":"91","author":"F Grosso","year":"2017","journal-title":"J Virol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2147\/OPTH.S207976","article-title":"Management of adenoviral keratoconjunctivitis: challenges and solutions","volume":"14","author":"B A Labib","year":"2020","journal-title":"Clin Ophthalmol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/1874285801610010004","article-title":"Pre-transplant screening for latent adenovirus in donors and recipients","volume":"10","author":"G Piatti","year":"2016","journal-title":"Open Microbiol J"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"L393","DOI":"10.1152\/ajplung.00359.2003","article-title":"Adenovirus vectors activate survival pathways in lung epithelial cells","volume":"287","author":"D M Flaherty","year":"2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref11","first-page":"1","article-title":"Adenoviruses types, cell receptors and local innate cytokines in adenovirus infection","volume":"33","author":"R Chen","year":"2013","journal-title":"Int Rev Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1002\/ptr.7039","article-title":"Medicinal plants: Treasure for antiviral drug discovery","volume":"35","author":"S I Ali","year":"2021","journal-title":"Phytother Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/ptr.895","article-title":"An antiviral principle present in a purified fraction from Melia azedarach L. leaf aqueous extract restrains Herpes simplex virus type 1 propagation","volume":"16","author":"L E Alch\u00e9","year":"2002","journal-title":"Phytother 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Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1515\/znc-2003-3-413","article-title":"An antiviral meliacarpin from leaves of Melia azedarach L","volume":"58","author":"L E Alch\u00e9","year":"2003","journal-title":"Z Naturforsch C J Biosci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.virusres.2008.12.013","article-title":"A natural tetranortriterpenoid with immunomodulatory properties as a potential anti-HSV agent","volume":"141","author":"C A Bueno","year":"2009","journal-title":"Virus Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbrc.2010.01.068","article-title":"A 1-Cinnamoyl-3, 11-di- hydroxymeliacarpin delays glycoprotein transport restraining virus multiplication without cytotoxicity","volume":"393","author":"C A Bueno","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/ptr.4974","article-title":"Effect of the potent antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin on cytokine production by murine macrophages stimulated with HSV-2","volume":"28","author":"E Petrera","year":"2014","journal-title":"Phytother Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1743-422X-3-45","article-title":"The synergistic effect of IFN-\u03b1 and IFN-\u03b3 against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin","volume":"3","author":"E Petrera","year":"2006","journal-title":"Virol J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.mvr.2012.09.003","article-title":"A natural antiviral and immunomodulatory compound with antiangiogenic properties","volume":"84","author":"C A Bueno","year":"2012","journal-title":"Microvasc 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Jennings","year":"2020","journal-title":"Microorganisms"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"105095","DOI":"10.1016\/j.bioorg.2021.105095","article-title":"Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1, 2-propanediol","volume":"114","author":"S Mazzotta","year":"2021","journal-title":"Bioorg Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10517-022-05390-w","article-title":"The effects of \u03b2-Pinene, a pine needle oil monoterpene, on adenovirus type 3","volume":"172","author":"B Qiu","year":"2022","journal-title":"Bull Exp Biol Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.32607\/20758251-2018-10-2-58-64","article-title":"1-(4-Phenoxybenzyl) 5-aminouracil derivatives and their analogues\u2013novel inhibitors of human adenovirus replication","volume":"37","author":"N A Nikitenko","year":"2018","journal-title":"Acta Naturae"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1021\/acs.jmedchem.9b01950","article-title":"Structure\u2212activity relationship studies on diversified salicylamide derivatives as potent inhibitors of human adenovirus infection","volume":"63","author":"J Xu","year":"2020","journal-title":"J Med Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S2468-1253(22)00199-6","article-title":"Use of cidofovir in recent outbreak of adenovirus-associated acute liver failure in children","volume":"7","author":"A Verma","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1055\/s-0030-1250648","article-title":"Gastroprotective effect and cytotoxicity of carnosic acid derivatives","volume":"77","author":"C Theoduloz","year":"2011","journal-title":"Planta Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1128\/jvi.71.1.398-404.1997","article-title":"Adenovirus infection stimulates the Raf\/MAPK signaling pathway interleukin-8 expression","volume":"71","author":"J T Bruder","year":"1997","journal-title":"J Virol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1158\/0008-5472.CAN-05-1484","article-title":"Adenovirus-induced extracellular signal-regulated kinase phosphorylation during the late phase of infection enhances viral protein levels and virus progeny","volume":"66","author":"M Sch\u00fcmann","year":"2006","journal-title":"Cancer Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1128\/JVI.78.8.4156-4164.2004","article-title":"Adenovirus type 7 induces interleukin-8 in a lung slice model and requires activation of Erk","volume":"78","author":"J L Booth","year":"2004","journal-title":"J Virol"},{"key":"ref39","first-page":"517","article-title":"Broad-spectrum antiviral agents","volume":"6","author":"J Zhu","year":"2015","journal-title":"Front Microbiol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.antiviral.2013.04.008","article-title":"Development of cellular signaling pathway inhibitors as new antivirals against influenza","volume":"98","author":"O Planz","year":"2013","journal-title":"Antiviral Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"108976","DOI":"10.1016\/j.cbi.2020.108976","article-title":"The genus Jatropha (Euphorbiaceae): A review on secondary chemical metabolites and biological aspects","volume":"318","author":"N B Cavalcante","year":"2020","journal-title":"Chem Biol Interact"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s11101-020-09667-8","article-title":"Jatrophane and rearranged jatrophane-type diterpenes: Biogenesis, structure, isolation, biological activity and SARs (1984\u20132019)","volume":"19","author":"M Fattahian","year":"2020","journal-title":"Phytochem Rev"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/tox.22925","article-title":"Anti-viral activity of jatrophone against RSV-induced respiratory infection via increase in interferon-\u03b3 generating dendritic cells","volume":"35","author":"K Li","year":"2020","journal-title":"Environ Toxicol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1021\/acs.jnatprod.2c00464","article-title":"Antiviral profiling of C-18- or C-19-functionalized semisynthetic Abietane diterpenoids","volume":"85","author":"M A Gonz\u00e1lez-Cardenete","year":"2022","journal-title":"J Nat Prod"}],"container-title":["Planta 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