­­­­Computational Identification of Taxus baccata-Derived Phytochemicals Targeting EZH2 to Overcome Therapeutic Resistance in Melanoma

­­­­Computational Identification of Taxus baccata-Derived Phytochemicals Targeting EZH2 to Overcome Therapeutic Resistance in Melanoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article ­­­­Computational Identification of Taxus baccata-Derived Phytochemicals Targeting EZH2 to Overcome Therapeutic Resistance in Melanoma Pritom Kundu, Musab Shahariar, Farzana Akter Munny, Anisha Tashruba Riya, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8494315/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Therapy resistance remains a significant challenge in melanoma treatment, despite recent advances in targeted therapies and immunotherapies. Enhancer of zeste homolog 2 (EZH2) has been identified as a critical target for overcoming resistance. However, the availability of effective inhibitors remains limited, emphasizing the need for novel therapeutic strategies to address this issue. This study aimed to identify potential EZH2 inhibitors derived from Taxus baccata using computational methods to overcome melanoma therapy resistance. A total of 98 phytochemical compounds from Taxus baccata were selected for in silico screening. The compounds were assessed using molecular docking to predict their binding affinities with EZH2. The pharmacokinetic properties of the compounds were evaluated using ADMET analysis, and Density Functional Theory (DFT) was used to assess their electronic properties. The top compounds were subjected to 100 ns molecular dynamics (MD) simulations to examine their stability and interaction dynamics, using tazemetostat and GSK-126 as reference inhibitors. Among the screened compounds, sotetsuflavone, ginkgetin, amentoflavone, and podocarpusflavone A were identified as potential EZH2 inhibitors. amentoflavone exhibited the highest binding affinity, strong interaction stability, and favorable pharmacokinetic profile. It also demonstrated the lowest negative binding free energy (MMPBSA), indicating a superior binding strength. These findings suggest that amentoflavone is the most promising candidate for further development, with the other compounds providing valuable scaffolds for optimization. This study provides a computational basis for designing novel EZH2 inhibitors from Taxus baccata . Further experimental validation is required to confirm these findings and explore the potential therapeutic applications of these phytochemicals in clinical settings. Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Therapy resistant Melanoma Phytochemicals Molecular Docking ADMET DFT MD Simulation Full Text Additional Declarations No competing interests reported. Supplementary Files SuplimentaryFile.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 May, 2026 Reviews received at journal 17 May, 2026 Reviews received at journal 13 May, 2026 Reviewers agreed at journal 08 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers invited by journal 20 Jan, 2026 Editor invited by journal 07 Jan, 2026 Editor assigned by journal 05 Jan, 2026 Submission checks completed at journal 05 Jan, 2026 First submitted to journal 01 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8494315","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":577437285,"identity":"e92d1267-4b82-4158-b2f1-7bbce2873b5f","order_by":0,"name":"Pritom Kundu","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Pritom","middleName":"","lastName":"Kundu","suffix":""},{"id":577437286,"identity":"aca573b3-ae2b-4072-94ed-de4963e45bb0","order_by":1,"name":"Musab Shahariar","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Musab","middleName":"","lastName":"Shahariar","suffix":""},{"id":577437287,"identity":"1a58184b-6225-4bb6-aa89-9150be4b4327","order_by":2,"name":"Farzana Akter Munny","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Farzana","middleName":"Akter","lastName":"Munny","suffix":""},{"id":577437288,"identity":"8039ed84-4f0c-4b81-b5b8-26948653b4e8","order_by":3,"name":"Anisha Tashruba Riya","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Anisha","middleName":"Tashruba","lastName":"Riya","suffix":""},{"id":577437289,"identity":"74919e67-acae-487e-909f-43fdbcbf5c0d","order_by":4,"name":"Hafeza Bhuiyan Lota","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Hafeza","middleName":"Bhuiyan","lastName":"Lota","suffix":""},{"id":577437290,"identity":"33880218-506d-4c51-bee4-ced7064d5365","order_by":5,"name":"Md. Zabir Ahmed","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Md.","middleName":"Zabir","lastName":"Ahmed","suffix":""},{"id":577437291,"identity":"452691ad-88be-41d5-99c9-e55378a13a8d","order_by":6,"name":"Mst.Afsana Meme","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Mst.Afsana","middleName":"","lastName":"Meme","suffix":""},{"id":577437293,"identity":"410dde1f-a573-400a-bff4-bb9451d3797f","order_by":7,"name":"Umme Mahfuza Parvin Kona","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Umme","middleName":"Mahfuza Parvin","lastName":"Kona","suffix":""},{"id":577437294,"identity":"d693cc07-140c-49c7-9f50-cd54d17dabc5","order_by":8,"name":"Fatema Mahmuda","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Fatema","middleName":"","lastName":"Mahmuda","suffix":""},{"id":577437296,"identity":"adbf5e74-5563-4ce6-a309-fc5a6c14c728","order_by":9,"name":"Shaima Saif Chowdhury","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Shaima","middleName":"Saif","lastName":"Chowdhury","suffix":""},{"id":577437299,"identity":"587d0b3b-6924-47fd-b629-f9bd547f4dfc","order_by":10,"name":"Sadia Afrin Sraboni","email":"","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":false,"prefix":"","firstName":"Sadia","middleName":"Afrin","lastName":"Sraboni","suffix":""},{"id":577437300,"identity":"95792547-7a8c-4f24-bfc2-08b50007b377","order_by":11,"name":"Md. Jubayer Hossain","email":"data:image/png;base64,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","orcid":"","institution":"Center for Health, Innovation, Research, Action, and Learning - Bangladesh","correspondingAuthor":true,"prefix":"","firstName":"Md.","middleName":"Jubayer","lastName":"Hossain","suffix":""}],"badges":[],"createdAt":"2026-01-01 09:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8494315/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8494315/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100861712,"identity":"b75c4608-11d9-42b7-8771-aa878d005ff5","added_by":"auto","created_at":"2026-01-22 07:46:24","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3402678,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/9778d0dd24d478de8399fbe8.png"},{"id":100861768,"identity":"d0688d98-41db-4742-b9ff-2a82b20ae692","added_by":"auto","created_at":"2026-01-22 07:46:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33632509,"visible":true,"origin":"","legend":"","description":"","filename":"EZH2ManuscriptNF.docx","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/76d2b736a7512c79da8d7777.docx"},{"id":100861874,"identity":"c6f3df9e-8490-4261-accb-3988eeeab815","added_by":"auto","created_at":"2026-01-22 07:46:58","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4414419,"visible":true,"origin":"","legend":"","description":"","filename":"Figure10.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/7eddc9fbb0bd0c51a5abbf4f.png"},{"id":100861807,"identity":"c13f0e11-1990-49ed-a228-2897618f469a","added_by":"auto","created_at":"2026-01-22 07:46:43","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":234726,"visible":true,"origin":"","legend":"","description":"","filename":"Figure11.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/aa1fe56238bf3ed1a4a328aa.png"},{"id":100861759,"identity":"8c5c7457-33b2-4cc0-9ccf-141fc35483ff","added_by":"auto","created_at":"2026-01-22 07:46:36","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":507289,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/2ef8bd349563449a25d90fa9.png"},{"id":100861985,"identity":"e93d4de9-a1bd-41ef-a0e7-d4b30ddd4123","added_by":"auto","created_at":"2026-01-22 07:47:16","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":275320,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/cdea128da3ec9f27e04d2b0b.png"},{"id":100861787,"identity":"2854a0f1-33ee-4f8b-b35b-b070b456b667","added_by":"auto","created_at":"2026-01-22 07:46:42","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18042348,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/6b571041cce1399933e64582.png"},{"id":100861698,"identity":"71a91ec1-63c1-44b2-81d1-5fc7b52993ee","added_by":"auto","created_at":"2026-01-22 07:46:21","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":67560,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/c435eb78ff6dc9503c521b68.png"},{"id":100861828,"identity":"41d85101-5ca1-472f-b957-86cb925be39c","added_by":"auto","created_at":"2026-01-22 07:46:46","extension":"jpg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142791,"visible":true,"origin":"","legend":"","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/82a8e10c36cbf3c3e068a075.jpg"},{"id":100861892,"identity":"c4727522-c20d-464a-a14b-bff4642a38fc","added_by":"auto","created_at":"2026-01-22 07:47:01","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3318916,"visible":true,"origin":"","legend":"","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/0712ecedbb2a7dd4c5524be3.png"},{"id":100861681,"identity":"d47828ae-4960-4a1a-85f6-13105809c488","added_by":"auto","created_at":"2026-01-22 07:46:17","extension":"jpg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4437438,"visible":true,"origin":"","legend":"","description":"","filename":"Figure8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/c84c4ac8ac1184c83b117ec8.jpg"},{"id":100861696,"identity":"f43cb35c-da43-4b14-8428-042fed068f06","added_by":"auto","created_at":"2026-01-22 07:46:21","extension":"jpg","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2117523,"visible":true,"origin":"","legend":"","description":"","filename":"Figure9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/7e51d3e81e2570f4211872ea.jpg"},{"id":100861820,"identity":"2ce423cf-7e12-4602-934c-73c8d5d77d69","added_by":"auto","created_at":"2026-01-22 07:46:45","extension":"json","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":13001,"visible":true,"origin":"","legend":"","description":"","filename":"67250dd9c1074587b7d75200db82a93f.json","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f303bca15b7817c376799388.json"},{"id":100861734,"identity":"16f187eb-60d3-4bf6-8220-dad3665becec","added_by":"auto","created_at":"2026-01-22 07:46:28","extension":"docx","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":120271,"visible":true,"origin":"","legend":"","description":"","filename":"SuplimentaryFile.docx","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/345992615dbebbe669b5faba.docx"},{"id":100861783,"identity":"44d28e83-0d6f-4134-bc1b-ca99c89015b6","added_by":"auto","created_at":"2026-01-22 07:46:42","extension":"pdf","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":307713,"visible":true,"origin":"","legend":"","description":"","filename":"SuplimentaryFile.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/bb2f94c6e3fdb337cea21c6f.pdf"},{"id":100861689,"identity":"d0133dfc-6822-4979-b1e2-210026f9b490","added_by":"auto","created_at":"2026-01-22 07:46:20","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":291339,"visible":true,"origin":"","legend":"","description":"","filename":"67250dd9c1074587b7d75200db82a93f1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/d88a5ca13fc0be8d1df4e20a.xml"},{"id":100861829,"identity":"3126c7a0-a7d4-450b-8a9c-62d336f8f9e3","added_by":"auto","created_at":"2026-01-22 07:46:46","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3402678,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/fe91cb34b4853250c2dcaac1.png"},{"id":100861717,"identity":"d06f6773-5624-4771-bce2-07004daaeb35","added_by":"auto","created_at":"2026-01-22 07:46:25","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4414419,"visible":true,"origin":"","legend":"","description":"","filename":"Figure10.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/5fb51f57a0cf310a83d76456.png"},{"id":100949834,"identity":"fd65ad1a-88ff-4deb-9369-bf56d7b78ce0","added_by":"auto","created_at":"2026-01-23 07:05:58","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":234726,"visible":true,"origin":"","legend":"","description":"","filename":"Figure11.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/154788817191c73289e94fee.png"},{"id":100861810,"identity":"e55e7706-cb14-4384-8bda-f4991790dbd4","added_by":"auto","created_at":"2026-01-22 07:46:43","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":507289,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/041b44039e41a34013248c7b.png"},{"id":100861772,"identity":"fefce86b-0eb2-42f2-a3e4-b264d4ad1b67","added_by":"auto","created_at":"2026-01-22 07:46:40","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":275320,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/e3b9c949055ebd34b9c2c5b1.png"},{"id":100861684,"identity":"cda2543e-3f41-479b-8831-3b3216aeca5b","added_by":"auto","created_at":"2026-01-22 07:46:19","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18042348,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/bed1d44899f64ed137f731c9.png"},{"id":100861704,"identity":"94cdf024-62a8-446f-9ccc-6540ae14d353","added_by":"auto","created_at":"2026-01-22 07:46:22","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":67560,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f09d3e462c9aa65231a9e0fe.png"},{"id":100861753,"identity":"162a211a-294d-451a-abf3-60a566b3b69a","added_by":"auto","created_at":"2026-01-22 07:46:35","extension":"jpg","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142791,"visible":true,"origin":"","legend":"","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f468a05d3074f3322df2808b.jpg"},{"id":100950248,"identity":"687eeb23-371e-466a-8248-980bed6abc7a","added_by":"auto","created_at":"2026-01-23 07:07:20","extension":"png","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3318916,"visible":true,"origin":"","legend":"","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/0b232bd80554a26663618b53.png"},{"id":100861771,"identity":"88ec0064-6d84-463e-8edf-ea8d836c9f90","added_by":"auto","created_at":"2026-01-22 07:46:39","extension":"jpg","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4437438,"visible":true,"origin":"","legend":"","description":"","filename":"Figure8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f2aa2c949e63a2d85ef8b487.jpg"},{"id":100861764,"identity":"b4d30841-4d22-481e-bd8b-256b17390a7f","added_by":"auto","created_at":"2026-01-22 07:46:38","extension":"jpg","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2117523,"visible":true,"origin":"","legend":"","description":"","filename":"Figure9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/090ab3c31ee22844c788541c.jpg"},{"id":100861683,"identity":"1de80489-7b0c-4e5c-9c38-08a5eb3607cf","added_by":"auto","created_at":"2026-01-22 07:46:19","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3402678,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/633e8a87af295224177a3893.png"},{"id":100861784,"identity":"bc2bb812-fdf1-4863-8cbd-6644b05c006e","added_by":"auto","created_at":"2026-01-22 07:46:42","extension":"jpeg","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2117523,"visible":true,"origin":"","legend":"","description":"","filename":"Figure9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/2386fe80f3a72299cc029baf.jpeg"},{"id":100861777,"identity":"4ea95fd5-ef79-4107-af7e-3f8c518f78e0","added_by":"auto","created_at":"2026-01-22 07:46:41","extension":"jpeg","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4414419,"visible":true,"origin":"","legend":"","description":"","filename":"Figure10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/45d82519398c9697f33b04ce.jpeg"},{"id":100861770,"identity":"accf3dc5-0c0f-4fec-9133-f2f5f67a91ff","added_by":"auto","created_at":"2026-01-22 07:46:39","extension":"jpeg","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":234726,"visible":true,"origin":"","legend":"","description":"","filename":"Figure11.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/0787aa03862ad4de767a3e14.jpeg"},{"id":100861774,"identity":"66093c46-e5ae-4ae9-bce5-2c1be7d726f5","added_by":"auto","created_at":"2026-01-22 07:46:40","extension":"png","order_by":31,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":507289,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/759f114e5bdac68349500ecc.png"},{"id":100861611,"identity":"ede35554-3cb8-4ec4-b01f-a33fcfd56fad","added_by":"auto","created_at":"2026-01-22 07:46:04","extension":"png","order_by":32,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":275320,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/7a2b8a5baf49d07af20c38cd.png"},{"id":100861869,"identity":"4e8a84d1-302e-4c86-b204-8626b9fb18e2","added_by":"auto","created_at":"2026-01-22 07:46:56","extension":"png","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18042348,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f9b61e0f1adc7cabdea4a225.png"},{"id":100861707,"identity":"7f756957-aac4-4086-8fea-98948ed6edfa","added_by":"auto","created_at":"2026-01-22 07:46:23","extension":"png","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":67560,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/ebffdd645b1fbbf66ba5cc94.png"},{"id":100861786,"identity":"96ce6007-8ddf-401e-8eb8-da5e33b47bce","added_by":"auto","created_at":"2026-01-22 07:46:42","extension":"jpeg","order_by":35,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142791,"visible":true,"origin":"","legend":"","description":"","filename":"Figure6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/7e477a04ab9054cea4b5e68d.jpeg"},{"id":100861814,"identity":"5cce9c61-90c8-4cf6-b86d-7286b5b099ff","added_by":"auto","created_at":"2026-01-22 07:46:44","extension":"jpeg","order_by":36,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1470665,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/d282bd399d39acce587c9135.jpeg"},{"id":100861769,"identity":"f5b81ffa-32e7-4cf4-9a31-ea8470803568","added_by":"auto","created_at":"2026-01-22 07:46:39","extension":"jpeg","order_by":37,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1638,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/d9040a4ebdb234e7d0d02a10.jpeg"},{"id":100861857,"identity":"bbe1d530-7b2b-4502-a4d6-24888c319bfc","added_by":"auto","created_at":"2026-01-22 07:46:52","extension":"jpeg","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1043591,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/40a5b03aecf58ceeacd36ae4.jpeg"},{"id":100861713,"identity":"ab7837d0-138c-4f54-9b1c-9be0e60d8a91","added_by":"auto","created_at":"2026-01-22 07:46:24","extension":"png","order_by":39,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":506891,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/a60ba98d6e329e6cde717b67.png"},{"id":100949526,"identity":"b8169517-1aa5-4730-b5f6-6abbfec12868","added_by":"auto","created_at":"2026-01-23 07:03:58","extension":"png","order_by":40,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":707457,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure10.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/8916057d4260ca6e894e77af.png"},{"id":100861809,"identity":"4f61126b-e979-40e6-aa27-64ad6de2cc12","added_by":"auto","created_at":"2026-01-22 07:46:43","extension":"png","order_by":41,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":260172,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure11.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/0e81f639d6298da4eeb4e1b5.png"},{"id":100861657,"identity":"9eb38acd-7009-4db3-8462-cb3756f2f4b3","added_by":"auto","created_at":"2026-01-22 07:46:13","extension":"png","order_by":42,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":110286,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/26aa743efb962610ec228737.png"},{"id":100861876,"identity":"0c6d1a68-a216-4a0c-a965-9e5dee367f9a","added_by":"auto","created_at":"2026-01-22 07:46:58","extension":"png","order_by":43,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130061,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/e7a47006be2456cdf3097155.png"},{"id":100861822,"identity":"e57dc8b3-9863-4126-ba89-2f226f1dba5e","added_by":"auto","created_at":"2026-01-22 07:46:45","extension":"png","order_by":44,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3045377,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/6d8fd8c4442d8363141e0169.png"},{"id":100861691,"identity":"812e750c-f191-4572-887d-2f1f7449de4e","added_by":"auto","created_at":"2026-01-22 07:46:20","extension":"png","order_by":45,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19152,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/706bc6b3a4130afcfa14b746.png"},{"id":100949742,"identity":"6a77c3ef-c0b5-427d-bd8c-500387db76d0","added_by":"auto","created_at":"2026-01-23 07:05:18","extension":"png","order_by":46,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114397,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure6.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/ef4e8cbe827b93af709d2aea.png"},{"id":100861623,"identity":"9ba098bd-37e9-4983-9eb1-e66149523c65","added_by":"auto","created_at":"2026-01-22 07:46:08","extension":"png","order_by":47,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":637932,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure7.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/e78a469e7bd216cf90a55236.png"},{"id":100861715,"identity":"0356a92a-a87a-4a7e-991d-24ed337c100c","added_by":"auto","created_at":"2026-01-22 07:46:25","extension":"png","order_by":48,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1998659,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure8.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/06f55e2b7ac7f031e5af0eca.png"},{"id":100861673,"identity":"ccbd5119-a2c4-4ffa-b840-8c63fa03f686","added_by":"auto","created_at":"2026-01-22 07:46:15","extension":"png","order_by":49,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1080155,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure9.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/924743a7b098381213666e1a.png"},{"id":100861894,"identity":"44b68566-bfb4-4da3-9273-27e86f7e450c","added_by":"auto","created_at":"2026-01-22 07:47:01","extension":"png","order_by":50,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":506891,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/1bf8610091099afdeea1fe6f.png"},{"id":100861850,"identity":"23ab24b7-abcc-4399-a1bc-524b2b37e76f","added_by":"auto","created_at":"2026-01-22 07:46:48","extension":"png","order_by":51,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1080155,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/63b01e860636dbf86863ee65.png"},{"id":100861695,"identity":"340ff265-d2ca-4609-979e-4d67d3395af1","added_by":"auto","created_at":"2026-01-22 07:46:21","extension":"png","order_by":52,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":707457,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/da6c7826dd86fbead4e49f36.png"},{"id":101880497,"identity":"ec60073a-57cd-4792-abf5-ccc56c7d380e","added_by":"auto","created_at":"2026-02-04 15:02:53","extension":"png","order_by":53,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":260172,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/cb2f4bae51bcfcdbd07f226a.png"},{"id":100861813,"identity":"5b5d9081-2517-4fa6-92e7-ea23c1c457e6","added_by":"auto","created_at":"2026-01-22 07:46:44","extension":"png","order_by":54,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":110286,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/65e496a01be687dc6476806b.png"},{"id":100861825,"identity":"2f3b9354-5b3f-4a57-a115-da544c1ed821","added_by":"auto","created_at":"2026-01-22 07:46:46","extension":"png","order_by":55,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130061,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/e3164318b89a20978def573e.png"},{"id":100861693,"identity":"eba7da9a-52c1-4f05-a3f9-2ecf0c73edbc","added_by":"auto","created_at":"2026-01-22 07:46:20","extension":"png","order_by":56,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3045377,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/57efebd0c0c2a4d76e22ebef.png"},{"id":100861762,"identity":"e3a22d9b-7a9b-4762-a3f9-ea657545f8e5","added_by":"auto","created_at":"2026-01-22 07:46:37","extension":"png","order_by":57,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19152,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/8b7329a3b7ac057c2e2a2974.png"},{"id":100861872,"identity":"73925b69-77d2-4168-abc9-bf8bf85b71b7","added_by":"auto","created_at":"2026-01-22 07:46:58","extension":"png","order_by":58,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114397,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/c1a6eed3e088bbb2a81722b3.png"},{"id":100861705,"identity":"7690057a-88e6-46e3-b9f5-b46d325aa96f","added_by":"auto","created_at":"2026-01-22 07:46:22","extension":"png","order_by":59,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":560228,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/f71fe12d9acb64d2c1f6912f.png"},{"id":100861811,"identity":"9a1e1f52-e01b-4003-868e-f0823c845f07","added_by":"auto","created_at":"2026-01-22 07:46:43","extension":"png","order_by":60,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":950,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/2b172227d6f623ccdffaa3f9.png"},{"id":100861746,"identity":"1e51aaca-3933-4bd9-9992-24f02b6cbd60","added_by":"auto","created_at":"2026-01-22 07:46:33","extension":"png","order_by":61,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":318709,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/9823417b2d9c6ff6009feaf4.png"},{"id":100949922,"identity":"9f2b8962-6854-4d58-9d1a-4c00df393daf","added_by":"auto","created_at":"2026-01-23 07:06:21","extension":"xml","order_by":62,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":291994,"visible":true,"origin":"","legend":"","description":"","filename":"67250dd9c1074587b7d75200db82a93f1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/ca4518905d46f9f9b7f5499c.xml"},{"id":100861721,"identity":"e02f0781-d291-4a0d-b0e8-7f40a5529e52","added_by":"auto","created_at":"2026-01-22 07:46:26","extension":"html","order_by":63,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":319881,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/e63be3b6af0892a68275f3dc.html"},{"id":101882715,"identity":"f9ee97c6-9be9-4b96-b7ce-284814ef3f11","added_by":"auto","created_at":"2026-02-04 15:24:41","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2306218,"visible":true,"origin":"","legend":"","description":"","filename":"EZH2ManuscriptNF.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1_covered_3d6ca18d-00f1-4d85-acbe-f9c589258860.pdf"},{"id":100861816,"identity":"49498244-00c5-4ec9-b872-3b295bcf2f81","added_by":"auto","created_at":"2026-01-22 07:46:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":120271,"visible":true,"origin":"","legend":"","description":"","filename":"SuplimentaryFile.docx","url":"https://assets-eu.researchsquare.com/files/rs-8494315/v1/a12aa402574f90ba99b1f3e1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"­­­­Computational Identification of Taxus baccata-Derived Phytochemicals Targeting EZH2 to Overcome Therapeutic Resistance in Melanoma","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Therapy resistant Melanoma, Phytochemicals, Molecular Docking, ADMET, DFT, MD Simulation","lastPublishedDoi":"10.21203/rs.3.rs-8494315/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8494315/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTherapy resistance remains a significant challenge in melanoma treatment, despite recent advances in targeted therapies and immunotherapies. Enhancer of zeste homolog 2 (EZH2) has been identified as a critical target for overcoming resistance. However, the availability of effective inhibitors remains limited, emphasizing the need for novel therapeutic strategies to address this issue. This study aimed to identify potential EZH2 inhibitors derived from \u003cem\u003eTaxus baccata\u003c/em\u003e using computational methods to overcome melanoma therapy resistance. A total of 98 phytochemical compounds from \u003cem\u003eTaxus baccata\u003c/em\u003e were selected for in silico screening. The compounds were assessed using molecular docking to predict their binding affinities with EZH2. The pharmacokinetic properties of the compounds were evaluated using ADMET analysis, and Density Functional Theory (DFT) was used to assess their electronic properties. The top compounds were subjected to 100 ns molecular dynamics (MD) simulations to examine their stability and interaction dynamics, using tazemetostat and GSK-126 as reference inhibitors. Among the screened compounds, sotetsuflavone, ginkgetin, amentoflavone, and podocarpusflavone A were identified as potential EZH2 inhibitors. amentoflavone exhibited the highest binding affinity, strong interaction stability, and favorable pharmacokinetic profile. It also demonstrated the lowest negative binding free energy (MMPBSA), indicating a superior binding strength. These findings suggest that amentoflavone is the most promising candidate for further development, with the other compounds providing valuable scaffolds for optimization. This study provides a computational basis for designing novel EZH2 inhibitors from \u003cem\u003eTaxus baccata\u003c/em\u003e. Further experimental validation is required to confirm these findings and explore the potential therapeutic applications of these phytochemicals in clinical settings.\u003c/p\u003e","manuscriptTitle":"­­­­Computational Identification of Taxus baccata-Derived Phytochemicals Targeting EZH2 to Overcome Therapeutic Resistance in Melanoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-22 07:38:13","doi":"10.21203/rs.3.rs-8494315/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-17T18:11:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-17T05:00:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:42:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319370639864122632743145701239899662174","date":"2026-05-08T04:32:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"50296457290290848942397010311754671852","date":"2026-05-07T21:02:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88301383938214235966438148649387522457","date":"2026-05-07T18:46:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"37745598507942254724244314336159388482","date":"2026-05-07T18:41:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-20T11:27:07+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-07T16:29:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T07:42:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-05T07:42:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-01-01T09:21:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16864653-8ee4-4278-8c88-d9e40610be7b","owner":[],"postedDate":"January 22nd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-17T18:11:33+00:00","index":100,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-17T05:00:19+00:00","index":99,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:42:56+00:00","index":98,"fulltext":""},{"type":"reviewerAgreed","content":"319370639864122632743145701239899662174","date":"2026-05-08T04:32:51+00:00","index":94,"fulltext":""},{"type":"reviewerAgreed","content":"50296457290290848942397010311754671852","date":"2026-05-07T21:02:35+00:00","index":92,"fulltext":""},{"type":"reviewerAgreed","content":"88301383938214235966438148649387522457","date":"2026-05-07T18:46:28+00:00","index":91,"fulltext":""},{"type":"reviewerAgreed","content":"37745598507942254724244314336159388482","date":"2026-05-07T18:41:43+00:00","index":90,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":61434640,"name":"Biological sciences/Cancer"},{"id":61434641,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":61434642,"name":"Biological sciences/Drug discovery"}],"tags":[],"updatedAt":"2026-01-22T07:38:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-22 07:38:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8494315","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8494315","identity":"rs-8494315","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}