{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:46:15Z","timestamp":1768873575989,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Repurposing off-label drugs during epidemics or pandemics with unknown\/known pathogens, particularly when their side effects and complications are already known, can be a strategic approach, as seen during the COVID-19 pandemic. Developing surrogate in vitro experimental models (passage-to-passage), which mimic epidemic\/pandemic-like transmission (human-to-human), may enhance this repurposing process. This study evaluates montelukast sodium (MLS), a US FDA-approved leukotriene receptor antagonist for asthma, to explore its potential repurposing antiviral effects against bovine respiratory syncytial virus (BRSV), which has basic similarities to human respiratory syncytial virus (HRSV) as both belong to the <jats:italic>Pneumoviridae<\/jats:italic> family.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>An in vitro serial passage model was developed using MDBK cells infected with a local wild-type strain of BRSV (43TR2018). The cytotoxicity of MLS was assessed via the trypan blue exclusion method, identifying non-toxic concentrations. The impact of MLS on viral spread and infectivity was measured through TCID50 values over 10 passages. Viral loads were confirmed by nested RT-PCR and quantified using qPCR, while apoptosis, necrosis, and nitric oxide production were evaluated through staining and nitrite assays. Data were analyzed using ANOVA and Tukey's test (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Control cells exhibited 97.16% viability, with 10\u00a0\u00b5M and 20\u00a0\u00b5M MLS concentrations maintaining viabilities of 89.2% and 87.3%, respectively. Viral titers significantly decreased at higher concentrations of MLS (up to 99.94% inhibition). Apoptosis rates decreased in MLS-treated cells, and live cell percentages improved, especially at 20\u00a0\u00b5M. Nitric oxide levels showed no significant differences across groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>MLS demonstrated a dose-dependent antiviral effect against BRSV, achieving 99% viral inhibition properties in MDBK cells. These promising results warrant further investigation into the antiviral mechanisms of MLS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12985-025-02647-4","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T03:49:06Z","timestamp":1739591346000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A surrogate in vitro experimental model for off-label drug repurposing: inhibitory effect of montelukast on bovine respiratory syncytial virus replication"],"prefix":"10.1186","volume":"22","author":[{"given":"Hanne Nur","family":"Kurucay","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zafer","family":"Yazici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vahide","family":"Bayrakal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahadir","family":"Muftuoglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emre","family":"Ozan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuneyt","family":"Tamer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seda","family":"Gozel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Barry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahir","family":"Igde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semra","family":"Okur-Gumusova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harun","family":"Albayrak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Eisa","family":"Elhag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huseyin","family":"Baskin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"2647_CR1","doi-asserted-by":"publisher","first-page":"145413","DOI":"10.1016\/j.scitotenv.2021.145413","volume":"767","author":"RM Beyer","year":"2021","unstructured":"Beyer RM, Manica A, Mora C. Shifts in global bat diversity suggest a possible role of climate change in the emergence of SARS-CoV-1 and SARS-CoV-2. Sci Total Environ. 2021;767:145413. https:\/\/doi.org\/10.1016\/j.scitotenv.2021.145413.","journal-title":"Sci Total Environ"},{"issue":"4","key":"2647_CR2","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/v13040667","volume":"13","author":"RJ Geraghty","year":"2021","unstructured":"Geraghty RJ, Aliota MT, Bonnac LF. Broad-spectrum antiviral strategies and nucleoside analogues. Viruses. 2021;13(4):667. https:\/\/doi.org\/10.3390\/v13040667.","journal-title":"Viruses"},{"key":"2647_CR3","doi-asserted-by":"publisher","DOI":"10.1177\/20587384211002621","author":"S Kausar","year":"2021","unstructured":"Kausar S, Said Khan F, Ishaq-Mujeeb-Ur-Rehman M, Akram M, Riaz M, Rasool G, Hami, et al. A review: mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol. 2021. https:\/\/doi.org\/10.1177\/20587384211002621.","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"9\u201310","key":"2647_CR4","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1159\/000518359","volume":"106","author":"M Dey","year":"2021","unstructured":"Dey M, Singh RK. Possible therapeutic potential of cysteinyl leukotriene receptor antagonist montelukast in treatment of SARS-CoV-2-Induced COVID-19. Pharmacology. 2021;106(9\u201310):469\u201376. https:\/\/doi.org\/10.1159\/000518359.","journal-title":"Pharmacology"},{"issue":"21","key":"2647_CR5","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.18410\/jebmh\/2021\/327","volume":"8","author":"PR Chakkarwar","year":"2021","unstructured":"Chakkarwar PR. Montelukast - its immuno-modulatory and antiviral action in COVID-19. J Evid Based Med Healthc. 2021;8(21):1731\u20132. https:\/\/doi.org\/10.18410\/jebmh\/2021\/327.","journal-title":"J Evid Based Med Healthc"},{"key":"2647_CR6","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.3389\/fmicb.2019.03079","volume":"10","author":"Y Chen","year":"2020","unstructured":"Chen Y, Li Y, Wang X, Zou P. Montelukast, an anti-asthmatic drug, inhibits zika virus infection by disrupting viral integrity. Front Microbiol. 2020;10:3079. https:\/\/doi.org\/10.3389\/fmicb.2019.03079.","journal-title":"Front Microbiol"},{"issue":"6","key":"2647_CR7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.2165\/00151829-200605060-00006","volume":"5","author":"D Fitzgerald","year":"2006","unstructured":"Fitzgerald D, Mellis C. Leukotriene receptor antagonists in virus-induced wheezing: evidence to date. Treat Respir Med. 2006;5(6):407\u201317. https:\/\/doi.org\/10.2165\/00151829-200605060-00006","journal-title":"Treat Respir Med"},{"issue":"2","key":"2647_CR8","doi-asserted-by":"publisher","first-page":"e00085","DOI":"10.1128\/mBio.00085-16","volume":"7","author":"S Landeras-Bueno","year":"2016","unstructured":"Landeras-Bueno S, Fern\u00e1ndez Y, Falc\u00f3n A, Oliveros JC, Ort\u00edn J. Chemical genomics \u0131dentifies the PERK-mediated unfolded protein stress response as a cellular target for \u0131nfluenza virus \u0131nhibition. MBio. 2016;7(2):e00085-e116. https:\/\/doi.org\/10.1128\/mBio.00085-16.","journal-title":"MBio"},{"key":"2647_CR9","doi-asserted-by":"publisher","first-page":"104996","DOI":"10.1016\/j.antiviral.2020.104996","volume":"185","author":"HJ Gan","year":"2021","unstructured":"Gan HJ, Harikishore A, Lee J, Jeon S, Rajan S, Chen MW, Neo JL, Kim S, Yoon HS. Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug. Antiviral Res. 2021;185:104996. https:\/\/doi.org\/10.1016\/j.antiviral.2020.104996.","journal-title":"Antiviral Res"},{"issue":"22","key":"2647_CR10","doi-asserted-by":"publisher","first-page":"10714","DOI":"10.1128\/jvi.74.22.10714-10728.2000","volume":"74","author":"JF Valarcher","year":"2000","unstructured":"Valarcher JF, Schelcher F, Bourhy H. Evolution of bovine respiratory syncytial virus. J Virol. 2000;74(22):10714\u201328. https:\/\/doi.org\/10.1128\/jvi.74.22.10714-10728.2000.","journal-title":"J Virol"},{"issue":"9","key":"2647_CR11","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.3390\/ani10091700","volume":"10","author":"Z Yazici","year":"2020","unstructured":"Yazici Z, Ozan E, Tamer C, Muftuoglu B, Barry G, Kurucay HN, Elhag AE, Cagirgan AA, Gumusova S, Albayrak H. Circulation of indigenous bovine respiratory syncytial virus strains in turkish cattle: the first isolation and molecular characterization. Animals. 2020;10(9):1700. https:\/\/doi.org\/10.3390\/ani10091700.","journal-title":"Animals"},{"issue":"3","key":"2647_CR12","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg. 1938;27(3):493\u20137. https:\/\/doi.org\/10.1093\/oxfordjournals.aje.a118408.","journal-title":"Am J Hyg"},{"issue":"8","key":"2647_CR13","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1111\/jfd.13629","volume":"45","author":"C Tamer","year":"2022","unstructured":"Tamer C, Benkaroun J, Kurucay HN, Albayrak H, Weidmann M. Development of a recombinase polymerase amplification assay for viral haemorrhagic septicemia virus. J Fish Dis. 2022;45(8):1065\u201371. https:\/\/doi.org\/10.1111\/jfd.13629.","journal-title":"J Fish Dis"},{"key":"2647_CR14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jviromet.2005.01.008","volume":"125","author":"M Boxus","year":"2005","unstructured":"Boxus M, Letellier C, Kerfhofs P. Real Time RT-PCR for the detection and quantitaion of bovine respiratory syncytial virus. J Virol Methods. 2005;125:125\u2013300. https:\/\/doi.org\/10.1016\/j.jviromet.2005.01.008.","journal-title":"J Virol Methods"},{"issue":"9","key":"2647_CR15","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1128\/jcm.32.9.2225-2231.1994","volume":"32","author":"S Vilcek","year":"1994","unstructured":"Vilcek S, Elvander M, Ballagy-Pordany A, Belak S. Development of nested PCR assays for detection of bovine respiratory syncytial virus in clinical samples. J Clin Microbiol. 1994;32(9):2225\u201331. https:\/\/doi.org\/10.1128\/jcm.32.9.2225-2231.1994.","journal-title":"J Clin Microbiol"},{"issue":"1","key":"2647_CR16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1182\/blood.V96.1.307","volume":"96","author":"E Shacter","year":"2000","unstructured":"Shacter E, Williams JA, Hinson RM, Sent\u00fcrker S, Lee YJ. Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis. Blood. 2000;96(1):307\u201313.\u00a0https:\/\/doi.org\/10.1182\/blood.V96.1.307","journal-title":"Blood"},{"issue":"Pt 1","key":"2647_CR17","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1099\/0022-1317-78-1-195","volume":"78","author":"H Baskin","year":"1997","unstructured":"Baskin H, Ellermann-Eriksen S, Lovmand J, Mogensen SC. Herpes simplex virus type 2 synergizes with interferon-gamma in the induction of nitric oxide production in mouse macrophages through autocrine secretion of tumour necrosis factor-alpha. J Gen Virol. 1997;78(Pt 1):195\u2013203. https:\/\/doi.org\/10.1099\/0022-1317-78-1-195.","journal-title":"J Gen Virol"},{"key":"2647_CR18","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ymeth.2022.02.004","volume":"203","author":"M Lazniewski","year":"2022","unstructured":"Lazniewski M, Dermawan D, Hidayat S, Muchtaridi M, Dawson WK, Plewczynski D. Drug repurposing for identification of potential spike inhibitors for SARS-CoV-2 using molecular docking and molecular dynamics simulations. Methods. 2022;203:498\u2013510. https:\/\/doi.org\/10.1016\/j.ymeth.2022.02.004.","journal-title":"Methods"},{"key":"2647_CR19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.nhtm.2014.12.002","volume":"2","author":"RJ Cohrs","year":"2015","unstructured":"Cohrs RJ, Martin T, Ghahramani P, Bidaut L, Higgins PJ, Shahzad A. Translational Medicine definition by the European Society for Translational Medicine. New Horiz Transl Med. 2015;2:86\u20138. https:\/\/doi.org\/10.1016\/j.nhtm.2014.12.002.","journal-title":"New Horiz Transl Med"},{"issue":"2","key":"2647_CR20","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1089\/ars.2011.4307","volume":"18","author":"RP Garofalo","year":"2013","unstructured":"Garofalo RP, Kolli D, Casola A. Respiratory syncytial virus \u0131nfection: mechanisms of redox control and novel therapeutic opportunities. Antioxid Redox Signal. 2013. https:\/\/doi.org\/10.1089\/ars.2011.4307.","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"2647_CR21","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1136\/jcp.23.1.7","volume":"23","author":"W Aherne","year":"1970","unstructured":"Aherne W, Bird T, Court SD, Gardner PS, McQuillin J. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol. 1970;23(1):7\u201318. https:\/\/doi.org\/10.1136\/jcp.23.1.7.","journal-title":"J Clin Pathol"},{"issue":"9","key":"2647_CR22","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1086\/344644","volume":"186","author":"HA Haeberle","year":"2002","unstructured":"Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich HJ, Van Rooijen N, et al. Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis. 2002;186(9):1199\u2013206. https:\/\/doi.org\/10.1086\/344644.","journal-title":"J Infect Dis"},{"issue":"5","key":"2647_CR23","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1128\/jvi.78.5.2232-2241.2004","volume":"78","author":"HA Haeberle","year":"2004","unstructured":"Haeberle HA, Casola A, Gatalica Z, Petronella S, Dieterich HJ, Ernst PB, et al. IkappaB kinase is a critical regulator of chemokine expression and lung inflammation in respiratory syncytial virus infection. J Virol. 2004;78(5):2232\u201341. https:\/\/doi.org\/10.1128\/jvi.78.5.2232-2241.2004.","journal-title":"J Virol"},{"key":"2647_CR24","unstructured":"(FDA) U.S. Food and Drug Administration. Montelukast sodium labeling information. Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2008\/021409s026lbl.pdf. Accessed 20 Jan 2025)"},{"key":"2647_CR25","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.csbj.2022.01.024","volume":"20","author":"M Luedemann","year":"2022","unstructured":"Luedemann M, Stadler D, Cheng CC, Protzer U, Knolle PA, Donakonda S. Montelukast is a dual-purpose inhibitor of SARS-CoV-2 infection and virus-induced IL-6 expression identified by structure-based drug repurposing. Comput Struct Biotechnol J. 2022;20:799\u2013811. https:\/\/doi.org\/10.1016\/j.csbj.2022.01.024.","journal-title":"Comput Struct Biotechnol J"},{"issue":"1","key":"2647_CR26","doi-asserted-by":"publisher","first-page":"197","DOI":"10.5897\/AJMR11.1326","volume":"6","author":"M Igde","year":"2012","unstructured":"Igde M, Yazici Z. Possible antiviral activity of montelukast against Herpes Simplex Virus type-1 and Human Adeno Virus in vitro. Afr J Microbiol Res. 2012;6(1):197\u2013202. https:\/\/doi.org\/10.5897\/AJMR11.1326.","journal-title":"Afr J Microbiol Res."},{"issue":"5","key":"2647_CR27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.3390\/v14050861","volume":"14","author":"Y Chen","year":"2022","unstructured":"Chen Y, Wang X, Shi H, Zou P. Montelukast inhibits HCoV-OC43 infection as a viral inactivator. Viruses. 2022;14(5):861. https:\/\/doi.org\/10.3390\/v14050861.","journal-title":"Viruses"},{"key":"2647_CR28","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.3390\/pharmaceutics15071891","volume":"15","author":"N Mulgaonkar","year":"2023","unstructured":"Mulgaonkar N, Wang H, Zhang J, Roundy CM, Tang W, Chaki SP, et al. Montelukast and telmisartan as inhibitors of SARS-CoV-2 omicron variant. Pharmaceutics. 2023;15:1891. https:\/\/doi.org\/10.3390\/pharmaceutics15071891.","journal-title":"Pharmaceutics"},{"key":"2647_CR29","doi-asserted-by":"publisher","first-page":"174196","DOI":"10.1016\/j.ejphar.2021.174196","volume":"904","author":"HM Al-Kuraishy","year":"2021","unstructured":"Al-Kuraishy HM, Al-Gareeb AI, Almulaiky YQ, Cruz-Martins N,\u00a0Batiha\u00a0GE. Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: the enigmatic entity. Eur J Pharmacol. 2021;904:174196. https:\/\/doi.org\/10.1016\/j.ejphar.2021.174196.","journal-title":"Eur J Pharmacol"},{"issue":"6","key":"2647_CR30","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/S1081-1206(10)61326-9","volume":"94","author":"S Maeba","year":"2005","unstructured":"Maeba S, Ichiyama T, Ueno Y, Makata H, Matsubara T, Furukawa S. Effect of montelukast on nuclear factor kappaB activation and proinflammatory molecules. Ann Allergy Asthma Immunol. 2005;94(6):670\u20134. https:\/\/doi.org\/10.1016\/S1081-1206(10)61326-9.","journal-title":"Ann Allergy Asthma Immunol"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-02647-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-025-02647-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-02647-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T15:33:13Z","timestamp":1739633593000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-025-02647-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2647"],"URL":"https:\/\/doi.org\/10.1186\/s12985-025-02647-4","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,15]]},"assertion":[{"value":"22 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors confirm that the ethical policies of the Journal, as stated on the Journal's author guidelines page, have been adhered to. No ethical approval was required, as no animals were culled or treated during this study, and all experiments were conducted using cell culture.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}