{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:05:55Z","timestamp":1773860755412,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Yellow fever (YF) is a mosquito\u2010borne virus with high mortality rates, affecting regions in South America and Africa. Despite the effectiveness of YF vaccines, increased global demand and reports of rare, severe side effects have spurred the search for safer therapeutic alternatives. Current treatments lack specific antiviral drugs approved for YF, underscoring the need for new, effective therapies. This study investigated the potential of <jats:italic>Passiflora edulis f. edulis<\/jats:italic> leaf and stem extracts as antiviral agents against the yellow fever virus (YFV). In vitro tests showed that the extracts significantly reduced YFV viral loads by twofold in Huh\u20107 cells and 1.5\u2010fold in Vero\u2010h\u2010Slam cells at a concentration of 50\u2009\u00b5g\/mL, with a smaller reduction at 25\u2009\u00b5g\/mL and no cytotoxic effects on either cell line. Phytochemical analysis identified a new C\u2010deoxyhexosyl flavone, luteolin\u20108\u2010(1\u2010<jats:italic>C<\/jats:italic>\u2010\u03b2\u2010boivinopyranosyl)\u20104\u20321\u2010<jats:italic>O<\/jats:italic>\u2010\u03b2\u2010<jats:sc>d<\/jats:sc>\u2010glucopyranoside, along with several known compounds. Protein\u2013protein interaction (PPI) network analysis using the STRING database and Cytoscape software revealed key hub genes, including IFNA1, IL7R, CD19, IL2RA, and IFNG, crucial in antiviral defense. Molecular docking studies further evaluated how these compounds interact with the YFV NS2B\u2010NS3 protease, essential for viral replication. Molecular dynamics (MD) simulations confirmed the stability of these interactions over a 120\u2010nanosecond period, supporting the compounds\u2019 antiviral potential. This study demonstrates the promise of <jats:italic>Passiflora edulis<\/jats:italic> metabolites as a foundation for developing novel YFV therapies by combining computational and experimental insights.<\/jats:p>","DOI":"10.1002\/ardp.202400853","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T13:55:12Z","timestamp":1739454912000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiviral metabolites from <i>Passiflora edulis<\/i>: An in vitro, phytochemical, and computational studies"],"prefix":"10.1002","volume":"358","author":[{"given":"Abeer H.","family":"Elmaidomy","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Teutsch","sequence":"additional","affiliation":[{"name":"Institute for Virology and Immunobiology University of W\u00fcrzburg Wuerzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-4091","authenticated-orcid":false,"given":"Jochen","family":"Bodem","sequence":"additional","affiliation":[{"name":"Institute for Virology and Immunobiology University of W\u00fcrzburg Wuerzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruqaiah I.","family":"Bedaiwi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk Tabuk Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mubarak A.","family":"Alzubaidi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6993-3325","authenticated-orcid":false,"given":"Hisham A.","family":"Abou\u2010Zied","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Deraya University Minia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-6922","authenticated-orcid":false,"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Deraya Center for Scientific Research Deraya University Minia Egypt"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(03)60009-6"},{"key":"e_1_2_8_3_1","unstructured":"A.Baier inFlavivirus Encephalitis 1st ed. (Ed: D. Ruzek) InTech Rijeka Croatia2011 104."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40409-018-0162-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.4.4.553"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2007.06.013"},{"issue":"07","key":"e_1_2_8_7_1","first-page":"701","volume":"33","author":"Xavier J. A.","year":"2022","journal-title":"J. Braz. Chem. Soc."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.52711\/0974-360X.2023.00247"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.10.009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/135965350300800201"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-62369-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17060759"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2003.07.014"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-873175"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-6-10"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2003.tb03431.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-8-1"},{"issue":"10","key":"e_1_2_8_18_1","first-page":"524","volume":"21","author":"Zhang B.","year":"1998","journal-title":"J. Chin. Med. Mater."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/095632020501600404"},{"issue":"10","key":"e_1_2_8_20_1","volume":"8","author":"Abubakr M.","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2005.05.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1076\/phbi.35.1.12.13264"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-259"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i11.2941"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15051211"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.57182\/jbiopestic.2.1.72-76"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x2020e10240"},{"issue":"2","key":"e_1_2_8_28_1","volume":"8","author":"G\u00f3mez L. A.","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0293"},{"issue":"4","key":"e_1_2_8_30_1","first-page":"128","volume":"24","author":"Okoye E.","year":"2012","journal-title":"Aust. J. Herb. Med."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(03)00175-X"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00617"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2012.07.101"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9422(99)00437-9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf970794"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44661-8"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02272159"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/la035719"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejlt.200300880"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-3084(98)00106-6"},{"issue":"1","key":"e_1_2_8_41_1","first-page":"D433","volume":"33","author":"Von Mering C.","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"issue":"1","key":"e_1_2_8_45_1","volume":"2","author":"Studio D.","year":"2008","journal-title":"Accelrys"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-023-05234-y"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.24890"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202400853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T22:57:16Z","timestamp":1741647436000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202400853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/ardp.202400853"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202400853","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400853"}}