{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:52:54Z","timestamp":1793303574621,"version":"4.5.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007950","name":"Tanta University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Chemistry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Molnupiravir (MOL) is a recently developed oral antiviral drug. MOL has been clinically evaluated for its efficacy against COVID-19. In this work, we utilize UV-absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence, molecular docking and molecular dynamic (MD) simulation to study the interaction between MOL and bovine serum albumin (BSA). The fluorescence spectroscopic analysis indicated that MOL effectively quenched the intrinsic fluorescence of BSA. To elucidate the fluorescence quenching mechanism, the interaction of MOL with BSA was examined at five distinct temperatures (285\u00a0K, 290\u00a0K, 295\u00a0K, 303\u00a0K and 308\u00a0K). The quenching constants diminished as the temperature increased, suggesting a static quenching mechanism, as evidenced by the Stern\u2013Volmer plots of F0\/F against the molar concentrations of MOL. This was further confirmed by UV absorption spectroscopy. Thermodynamic analysis revealed a 1:1 stoichiometry for MOL binding to BSA, with a negative Gibbs free energy change (\u0394G), confirming the spontaneous nature of binding. Competitive binding experiments using site-specific markers as well as molecular docking studies showed that MOL binds to site II. Synchronous fluorescence spectroscopy indicated that MOL was binding around tyrosine (Tyr) residues of the protein. These findings were further confirmed by the molecular docking and MD simulation studies. This research could provide valuable insights into the pharmacokinetics and pharmacodynamics of MOL, which could contribute to the development of more effective antiviral drugs.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s13065-025-01645-5","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T13:30:29Z","timestamp":1761571829000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi spectroscopic investigations with molecular docking and molecular dynamics simulation of the binding mechanism of molnupiravir to bovine serum albumin"],"prefix":"10.1186","volume":"19","author":[{"given":"Fotouh R.","family":"Mansour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Elhosary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar H.","family":"Elagamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Barseem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira H.","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"1645_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26195795","author":"M Imran","year":"2021","unstructured":"Imran M, Kumar Arora M, Asdaq SMB, Khan SA, Alaqel SI, Alshammari MK, Alshehri MM, Alshrari AS, Mateq Ali A, Al-Shammeri AM, Alhazmi BD, Harshan AA, Alam MT. Abida, Discovery, development, and patent trends on molnupiravir: a prospective oral treatment for covid-19. Molecules. 2021. https:\/\/doi.org\/10.3390\/molecules26195795","journal-title":"Molecules"},{"key":"1645_CR2","doi-asserted-by":"publisher","first-page":"102329","DOI":"10.1016\/j.dsx.2021.102329","volume":"15","author":"AK Singh","year":"2021","unstructured":"Singh AK, Singh A, Singh R, Misra A. Molnupiravir in COVID-19: a systematic review of literaturef. Diabetes Metab Syndr Clin Res Rev. 2021;15:102329. https:\/\/doi.org\/10.1016\/j.dsx.2021.102329.","journal-title":"Diabetes Metab Syndr Clin Res Rev"},{"key":"1645_CR3","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s40265-022-01684-5","volume":"82","author":"YY Syed","year":"2022","unstructured":"Syed YY. Molnupiravir: first approval. Drugs. 2022;82:455\u201360. https:\/\/doi.org\/10.1007\/s40265-022-01684-5.","journal-title":"Drugs"},{"key":"1645_CR4","doi-asserted-by":"publisher","first-page":"102396","DOI":"10.1016\/j.dsx.2022.102396","volume":"16","author":"AK Singh","year":"2022","unstructured":"Singh AK, Singh A, Singh R, Misra A. An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19, diabetes metab. Syndr Clin Res Rev. 2022;16:102396. https:\/\/doi.org\/10.1016\/j.dsx.2022.102396.","journal-title":"Syndr Clin Res Rev"},{"key":"1645_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/cts.13732","volume":"17","author":"BM Maas","year":"2024","unstructured":"Maas BM, Strizki J, Miller RR, Kumar S, Brown M, Johnson MG, Cheng M, De Anda C, Rizk ML, Stone JA. Molnupiravir: mechanism of action. Clin Transl Sci. 2024; 17: 1\u20138. https:\/\/doi.org\/10.1111\/cts.13732","journal-title":"Clin Transl Sci"},{"key":"1645_CR6","doi-asserted-by":"crossref","unstructured":"Schreiber S. Special articles serum albumin liver. 1988;8:385\u2013401.","DOI":"10.1002\/hep.1840080234"},{"key":"1645_CR7","doi-asserted-by":"publisher","first-page":"116200","DOI":"10.1016\/j.molliq.2021.116200","volume":"336","author":"S Siddiqui","year":"2021","unstructured":"Siddiqui S, Ameen F, ur Rehman S, Sarwar T, Tabish M. Studying the interaction of drug\/ligand with serum albumin. J Mol Liq. 2021;336:116200.","journal-title":"J Mol Liq"},{"key":"1645_CR8","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.saa.2015.12.003","volume":"156","author":"Q Wang","year":"2016","unstructured":"Wang Q, Huang C, Jiang M, Zhu Y, Wang J, Chen J, Shi J. Binding interaction of Atorvastatin with bovine serum albumin: spectroscopic methods and molecular docking. Spectrochim Acta part A mol Biomol Spectrosc. 2016;156:155\u201363.","journal-title":"Spectrochim.Acta part A mol Biomol Spectrosc"},{"key":"1645_CR9","first-page":"215","volume":"87","author":"T Topal\\ua","year":"2014","unstructured":"Topal\\ua T, Bodoki A, Oprean L, Oprean R. Bovine serum albumin interactions with metal complexes. Clujul Med. 2014;87:215.","journal-title":"Clujul Med"},{"key":"1645_CR10","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jpha.2015.07.001","volume":"6","author":"VD Suryawanshi","year":"2016","unstructured":"Suryawanshi VD, Walekar LS, Gore AH, Anbhule PV, Kolekar GB. Spectroscopic analysis on the binding interaction of biologically active pyrimidine derivative with bovine serum albumin. J Pharm Anal. 2016;6:56\u201363. https:\/\/doi.org\/10.1016\/j.jpha.2015.07.001.","journal-title":"J Pharm Anal"},{"key":"1645_CR11","doi-asserted-by":"publisher","first-page":"114693","DOI":"10.1016\/j.jpba.2022.114693","volume":"214","author":"T Re\u00e7ber","year":"2022","unstructured":"Re\u00e7ber T, Timur SS, Kablan SE, Yal\u00e7\\in F, Karabulut TC, G\u00fcrsoy RN, Ero\\uglu H, K\\ir S, Nemutlu E. A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies. J Pharm Biomed Anal. 2022;214:114693.","journal-title":"J Pharm Biomed Anal"},{"key":"1645_CR12","first-page":"2300213","volume":"10","author":"AM Annadi","year":"2022","unstructured":"Annadi AM, El Zahar NM, Abdel-Sattar NE-DA, Mohamed EH, Mahmoud SA, Attia MS. Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method. Sep Sci Plus. 2022;10:2300213.","journal-title":"Sep Sci Plus"},{"key":"1645_CR13","doi-asserted-by":"publisher","DOI":"10.18103\/mra.v10i9.3127","author":"G Camlik","year":"2022","unstructured":"Camlik G, Beyazaslan F, Kara E, Ulker D, Albayrak I, Degim IT. A validated high-pressure liquid chromatography (HPLC) method for molnupiravir. Med Res Arch. 2022. https:\/\/doi.org\/10.18103\/mra.v10i9.3127.","journal-title":"Med Res Arch"},{"key":"1645_CR14","doi-asserted-by":"publisher","first-page":"580","DOI":"10.30574\/wjarr.2022.15.1.0720","volume":"15","author":"M Bindu","year":"2022","unstructured":"Bindu M, Gandla K, Vemireddy S, Samuel S, Praharsha Y. A validated stability indicating RP-HPLC method for the determination of molnupiravir in pharmaceutical dosage form. World J Adv Res Rev. 2022;15:580\u201390.","journal-title":"World J Adv Res Rev"},{"key":"1645_CR15","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.3390\/biomedicines11092356","volume":"11","author":"T Komarov","year":"2023","unstructured":"Komarov T, Karnakova P, Archakova O, Shchelgacheva D, Bagaeva N, Popova M, Karpova P, Zaslavskaya K, Bely P, Shohin I. Development and validation of a High-Performance liquid chromatography with tandem mass spectrometry (HPLC-MS\/MS) method for quantification of major molnupiravir metabolite ($\u03b2$-D-N4-hydroxycytidine) in human plasma. Biomedicines. 2023;11:2356.","journal-title":"Biomedicines"},{"key":"1645_CR16","doi-asserted-by":"publisher","first-page":"123363","DOI":"10.1016\/j.jchromb.2022.123363","volume":"1206","author":"AS Gouda","year":"2022","unstructured":"Gouda AS, Marzouk HM, Rezk MR, Salem AM, Morsi MI, Nouman EG, Abdallah YM, Hassan AY, Abdel-Megied AM. A validated LC-MS\/MS method for determination of antiviral prodrug molnupiravir in human plasma and its application for a Pharmacokinetic modeling study in healthy Egyptian volunteers. J Chromatogr B. 2022;1206:123363.","journal-title":"J Chromatogr B"},{"key":"1645_CR17","doi-asserted-by":"publisher","first-page":"114356","DOI":"10.1016\/j.jpba.2021.114356","volume":"206","author":"A Amara","year":"2021","unstructured":"Amara A, Penchala SD, Else L, Hale C, FitzGerald R, Walker L, Lyons R, Fletcher T, Khoo S. The development and validation of a novel LC-MS\/MS method for the simultaneous quantification of molnupiravir and its metabolite \u00df-d-N4-hydroxycytidine in human plasma and saliva. J Pharm Biomed Anal. 2021;206:114356.","journal-title":"J Pharm Biomed Anal"},{"key":"1645_CR18","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1080\/10826076.2022.2063331","volume":"44","author":"S Jain","year":"2021","unstructured":"Jain S, Giri S, Sharma N, Shah RP. LC and LC-HRMS studies on stability behavior of molnupiravir an anti-COVID 19 drug. J Liq Chromatogr \\& Relat Technol. 2021;44:750\u20139.","journal-title":"J Liq Chromatogr \\& Relat Technol"},{"key":"1645_CR19","first-page":"110397","volume":"200","author":"RE Kannouma","year":"2024","unstructured":"Kannouma RE, Kamal AH, Hammad MA, Mansour FR. Incorporation of eggshell waste in the Preparation of carbon quantum Dot nanoprobes for the determination of COVID-19 antiviral drug; molnupiravir, microchem. J. 2024;200:110397.","journal-title":"J"},{"key":"1645_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13065-023-00933-2","volume":"17","author":"AR Mohamed","year":"2023","unstructured":"Mohamed AR, Abolmagd E, Nour IM, Badrawy M, Hasan MA. Earth-friendly-assessed silver-nanoparticles spectrophotometric method for rapid and sensitive analysis of Molnupiravir, an FDA-approved candidate for COVID-19: application on pharmaceutical formulation and dissolution test. BMC Chem. 2023;17:13.","journal-title":"BMC Chem"},{"key":"1645_CR21","doi-asserted-by":"publisher","first-page":"11237","DOI":"10.3390\/ijms241411237","volume":"24","author":"\u00c9 Bakos","year":"2023","unstructured":"Bakos \u00c9, Temesszentandr\u00e1si-Ambrus C, \u00d6zvegy-Laczka C, G\u00e1borik Z, Sarkadi B, Telbisz \u00c1. Interactions of the Anti-SARS-CoV-2 agents molnupiravir and Nirmatrelvir\/Paxlovid with human drug transporters. Int J Mol Sci. 2023;24:11237.","journal-title":"Int J Mol Sci"},{"key":"1645_CR22","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.3390\/ijms24032849","volume":"24","author":"O D\u00f6m\u00f6t\u00f6r","year":"2023","unstructured":"D\u00f6m\u00f6t\u00f6r O, Enyedy \u00c9A. Evaluation of in vitro distribution and plasma protein binding of selected antiviral drugs (favipiravir, molnupiravir and imatinib) against SARS-CoV-2. Int J Mol Sci. 2023;24:2849.","journal-title":"Int J Mol Sci"},{"key":"1645_CR23","doi-asserted-by":"publisher","first-page":"115448","DOI":"10.1016\/j.jpba.2023.115448","volume":"233","author":"VM Trusova","year":"2023","unstructured":"Trusova VM, Zhytniakivska OA, Tarabara UK, Vus KA, Gorbenko GP. Deciphering the molecular details of interactions between anti-COVID drugs and functional human proteins: in Silico approach. J Pharm Biomed Anal. 2023;233:115448.","journal-title":"J Pharm Biomed Anal"},{"key":"1645_CR24","first-page":"101","volume":"14","author":"S Begum","year":"2025","unstructured":"Begum S, D UR, Somanjeri N, Taj SN, Begum S, D UR, Somanjeri N, Taj SN. Exploring the molecular level interactions of molnupiravir with serum Albumin- an analytical Approach, biochem. Biophys Res Commun. 2025;14:101\u20137.","journal-title":"Biophys Res Commun"},{"key":"1645_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2021.120298","author":"MA Abdelaziz","year":"2022","unstructured":"Abdelaziz MA, Shaldam M, El-Domany RA, Belal F. Multi-Spectroscopic, thermodynamic and molecular dynamic simulation studies for investigation of interaction of Dapagliflozin with bovine serum albumin, spectrochim. Acta - Part Mol Biomol Spectrosc. 2022. https:\/\/doi.org\/10.1016\/j.saa.2021.120298.","journal-title":"Acta - Part Mol Biomol Spectrosc"},{"issue":"16","key":"1645_CR26","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. Software news and updates AutoDock4 and AutoDockTools4: automated Docking with selective receptor flexibility. J Comput Chem. 2009;30(16):2785\u201391.","journal-title":"J Comput Chem"},{"key":"1645_CR27","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1002\/prot.24583","volume":"82","author":"A Bujacz","year":"2014","unstructured":"Bujacz A, Zielinski K, Sekula B. Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen, proteins struct. Funct Bioinforma. 2014;82:2199\u2013208.","journal-title":"Funct Bioinforma"},{"key":"1645_CR28","volume-title":"Fluorescence spectroscopy in biology advanced methods and their applications to membranes, proteins, DNA, and cells","author":"M Hof","year":"2004","unstructured":"Hof M, Hutterer R, Fidler V. Fluorescence spectroscopy in biology advanced methods and their applications to membranes, proteins, DNA, and cells. Berlin: Springer Science & Business Media; 2004."},{"key":"1645_CR29","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1021\/cr0404390","volume":"106","author":"CA Royer","year":"2006","unstructured":"Royer CA. Probing protein folding and conformational transitions with fluorescence. Chem Rev. 2006;106:1769\u201384.","journal-title":"Chem Rev"},{"key":"1645_CR30","doi-asserted-by":"publisher","unstructured":"Lakowicz JR. Principles of fluorescence spectroscopy;1983. https:\/\/doi.org\/10.1007\/978-1-4615-7658-7","DOI":"10.1007\/978-1-4615-7658-7"},{"key":"1645_CR31","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.envpol.2011.10.026","volume":"161","author":"B Pan","year":"2012","unstructured":"Pan B, Liu Y, Xiao D, Wu F, Wu M, Zhang D, Xing B. Quantitative identification of dynamic and static quenching of Ofloxacin by dissolved organic matter using temperature-dependent kinetic approach. Environ Pollut. 2012;161:192\u20138.","journal-title":"Environ Pollut"},{"key":"1645_CR32","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jlumin.2016.01.029","volume":"175","author":"K Ghosh","year":"2016","unstructured":"Ghosh K, Rathi S, Arora D. Fluorescence spectral studies on interaction of fluorescent probes with bovine serum albumin (BSA). J Lumin. 2016;175:135\u201340.","journal-title":"J Lumin"},{"key":"1645_CR33","doi-asserted-by":"publisher","first-page":"110535","DOI":"10.1016\/j.dyepig.2022.110535","volume":"205","author":"X-X Lang","year":"2022","unstructured":"Lang X-X, Li H-Y, Cao H-W, Chen Y-S, Zhang P-X, Wang H-J, Wang M-Q. Exploring the binding mechanism of amine-functionalized tetraaryl imidazole fluorescent ligands with lipase: insights from multi-spectroscopic, thermodynamic and Docking approaches. Dye Pigment. 2022;205:110535.","journal-title":"Dye Pigment"},{"key":"1645_CR34","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jphotobiol.2016.06.025","volume":"162","author":"J Shi","year":"2016","unstructured":"Shi J, Pan D, Wang X, Liu T-T, Jiang M, Wang Q. Characterizing the binding interaction between antimalarial Artemether (AMT) and bovine serum albumin (BSA): spectroscopic and molecular Docking methods. J Photochem Photobiol B Biol. 2016;162:14\u201323.","journal-title":"J Photochem Photobiol B Biol"},{"key":"1645_CR35","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.3390\/ijms20112727","volume":"20","author":"S Rahman","year":"2019","unstructured":"Rahman S, Rehman MT, Rabbani G, Khan P, AlAjmi MF, Hassan MI, Muteeb G, Kim J. Insight of the interaction between 2, 4-thiazolidinedione and human serum albumin: A spectroscopic, thermodynamic and molecular Docking study. Int J Mol Sci. 2019;20:2727.","journal-title":"Int J Mol Sci"},{"key":"1645_CR36","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1002\/bio.4270","volume":"37","author":"F Belal","year":"2022","unstructured":"Belal F, Mabrouk M, Hammad S, Barseem A, Ahmed H. Multi-spectroscopic, thermodynamic and molecular Docking studies to investigate the interaction of eplerenone with human serum albumin. Luminescence. 2022;37:1162\u201373.","journal-title":"Luminescence"},{"key":"1645_CR37","doi-asserted-by":"publisher","first-page":"e01434","DOI":"10.1128\/aac.01434-24","volume":"69","author":"JL Fiore","year":"2025","unstructured":"Fiore JL, Jin Y, Heimbach T, Patel SR, Zhao T, .Matthews CZ, Pagnussat S, Maas BM, Cheng MH. Pharmacokinetics and bioequivalence of a molnupiravir tablet formulation compared with the molnupiravir capsule formulation in healthy adult participants\u2014a randomized, open-label, three-period, crossover study. Antimicrob Agents Chemother. 2025;69:e01434\u201324.","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"1645_CR38","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1111\/cts.13602","volume":"16","author":"M Iwamoto","year":"2023","unstructured":"Iwamoto M, Duncan KE, Wickremasingha PK, Zhao, T, Liberti MV, Lemoine L, Decaesteker T, Rottey S, Maas BM, Gillespie G. Assessment of pharmacokinetics, safety, and tolerability following twice-daily administration of molnupiravir for 10 days in healthy participants. Clin Transl Sci. 2023;16(10):1947\u201356.","journal-title":"Clin Transl Sci"}],"container-title":["BMC Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13065-025-01645-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13065-025-01645-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13065-025-01645-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:08:54Z","timestamp":1761847734000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcchem.biomedcentral.com\/articles\/10.1186\/s13065-025-01645-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1645"],"URL":"https:\/\/doi.org\/10.1186\/s13065-025-01645-5","relation":{},"ISSN":["2661-801X"],"issn-type":[{"value":"2661-801X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]},"assertion":[{"value":"27 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 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":"Not applicable.","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":"286"}}