{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:56:38Z","timestamp":1785336998951,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The two most clinically important members of the flavivirus genus, Zika virus (ZIKV) and dengue virus (DENV) pose a significant public health challenge. They cause a range of diseases in humans, from hemorrhagic to neurological manifestations, leading to economic and social burden worldwide. Nevertheless, there are no approved antiviral drugs to treat these infections. Zafirlukast is an orally available Food and Drug Administration (FDA) approved drug for the prophylaxis and treatment of chronic asthma. It is a leukotriene receptor antagonist (LTRA) with high selectivity of the cysteinyl leukotriene\u20101 receptor (CYSLTR1) that acts as an immune modulator. Thus, we evaluated the antiviral potential of Zafirlukast against ZIKV and DENV in SK\u2010N\u2010SH cells. We showed that Zafirlukast exhibited potent antiviral activity against ZIKV, which could be linked to Zafirlukast's immune blockade of TNF signaling pathways and its downstream signaling pathways such as MAPK and ERK1\/2. In addition, our results showed that Zafirlukast also counteracts ZIKV\u2010induced changes in key genes involved in cellular lipid metabolism. Thus, these findings highlight the translational potential of optimizing Zafirlukast as a therapeutic agent for the treatment of ZIKV and DENV.<\/jats:p>","DOI":"10.1002\/jmv.70144","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T10:38:57Z","timestamp":1735641537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiviral and Immunomodulatory Effects of Zafirlukast Against Flaviviruses via Inhibition of the TNF Signaling Pathway"],"prefix":"10.1002","volume":"97","author":[{"given":"Thamil Vaani","family":"Komarasamy","sequence":"first","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gilbert\u2010Jaramillo","sequence":"additional","affiliation":[{"name":"James &amp; Lillian Martin Centre, Sir William Dunn School of Pathology University of Oxford Oxford UK"},{"name":"Oxford Motor Neuron Disease Centre Nuffield Department of Clinical Neurosciences John Radcliffe Hospital, University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Amelia Azreen","family":"Adnan","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"James","sequence":"additional","affiliation":[{"name":"James &amp; Lillian Martin Centre, Sir William Dunn School of Pathology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-307X","authenticated-orcid":false,"given":"Vinod RMT.","family":"Balasubramaniam","sequence":"additional","affiliation":[{"name":"Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1608612"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1602708"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-2038D"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.08.035"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.55"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0625-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-020-02284-w"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2020.2762"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13337-022-00795-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800820"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(23)00522-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.03079"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/1062936X.2021.1993995"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00085-16"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aao1680"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0009183"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12748"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2001.tb01575.x"},{"issue":"3","key":"e_1_2_8_21_1","first-page":"172","article-title":"Cytokine Patterns During Dengue Shock Syndrome","volume":"14","author":"Suharti C.","year":"2003","journal-title":"European Cytokine Network"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/314680"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052215"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.279"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00792-3"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02460-8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar2749"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200109)31:9<2566::AID-IMMU2566>3.0.CO;2-L"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30858-8"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16717"},{"key":"e_1_2_8_31_1","volume-title":"StatPearls Treasure Island","author":"Gerriets V.","year":"2020"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.059889"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T08:26:27Z","timestamp":1741767987000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,31]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/jmv.70144"],"URL":"https:\/\/doi.org\/10.1002\/jmv.70144","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,31]]},"assertion":[{"value":"2024-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70144"}}