Computational identification of Glycyrrhiza glabra-derived Semilicoisoflavone B and Licoisoflavone B as dual-target inhibitors of Ebola virus proteins

Computational identification of Glycyrrhiza glabra-derived Semilicoisoflavone B and Licoisoflavone B as dual-target inhibitors of Ebola virus proteins | 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 Glycyrrhiza glabra-derived Semilicoisoflavone B and Licoisoflavone B as dual-target inhibitors of Ebola virus proteins Fahad Fardin, Md. Al-Amin, Abir Hossain, Moshammat Nasrin Akter, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9179366/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Ebola virus disease (EVD) is a life-threatening zoonotic infection caused by the Ebola virus (EBOV), characterized by high mortality rates and persistent global health concern, with no FDA-approved small-molecule therapeutics currently available. This study investigated Glycyrrhiza glabra phytochemicals as promising dual-target inhibitors of two essential EBOV proteins: matrix protein VP40 and nucleoprotein (NP). An integrated in-silico approach comprising molecular docking, ADMET profiling, 100 ns molecular dynamics simulations, principal component analysis, and density functional theory calculations was employed. Virtual screening of 408 phytocompounds identified two G. glabra -derived phytocompounds, Semilicoisoflavone B and Licoisoflavone B, as promising candidates, exhibiting superior binding affinities (VP40: −10.6 to −9.7 kcal/mol; NP: −9.2 to −8.8 kcal/mol) compared to control ligands Laurifolin and Licochalcone A. Both phytocompounds were identified as promising inhibitors, exhibiting strong binding affinity for both target proteins and favorable pharmacokinetics. Molecular dynamics simulations confirmed stable protein-ligand interactions, with Semilicoisoflavone B showing exceptional affinity for VP40 (ΔG = −129.21 kcal/mol). PCA revealed constrained conformational dynamics, while density functional theory analysis demonstrated favorable electronic properties including narrow HOMO-LUMO gaps (3.69–4.21 eV). These findings suggest Semilicoisoflavone B and Licoisoflavone B as promising dual-target inhibitors of the VP40 and NP of the EBOV; however, further in-vitro and in-vivo studies are necessary to evaluate their therapeutic efficacy. Biological sciences/Biochemistry Physical sciences/Chemistry Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Ebola virus VP40 matrix protein Nucleoprotein Glycyrrhiza glabra Phytocompounds Molecular docking Dynamics simulation Antiviral therapeutics Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 12 May, 2026 Reviewers agreed at journal 09 May, 2026 Reviews received at journal 03 May, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviews received at journal 22 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers invited by journal 01 Apr, 2026 Editor assigned by journal 27 Mar, 2026 Editor invited by journal 27 Mar, 2026 Submission checks completed at journal 23 Mar, 2026 First submitted to journal 23 Mar, 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. 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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-9179366","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":616058939,"identity":"089cf017-1d1e-4b73-9cc9-a474c50cf6a1","order_by":0,"name":"Fahad Fardin","email":"","orcid":"","institution":"Jahangirnagar University","correspondingAuthor":false,"prefix":"","firstName":"Fahad","middleName":"","lastName":"Fardin","suffix":""},{"id":616058941,"identity":"6391f0fb-58c5-428b-94c0-4e06d79b99bb","order_by":1,"name":"Md. 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This study investigated \u003cem\u003eGlycyrrhiza glabra\u003c/em\u003e phytochemicals as promising dual-target inhibitors of two essential EBOV proteins: matrix protein VP40 and nucleoprotein (NP). An integrated \u003cem\u003ein-silico\u003c/em\u003e approach comprising molecular docking, ADMET profiling, 100 ns molecular dynamics simulations, principal component analysis, and density functional theory calculations was employed. Virtual screening of 408 phytocompounds identified two \u003cem\u003eG. glabra\u003c/em\u003e -derived phytocompounds, Semilicoisoflavone B and Licoisoflavone B, as promising candidates, exhibiting superior binding affinities (VP40: −10.6 to −9.7 kcal/mol; NP: −9.2 to −8.8 kcal/mol) compared to control ligands Laurifolin and Licochalcone A. Both phytocompounds were identified as promising inhibitors, exhibiting strong binding affinity for both target proteins and favorable pharmacokinetics. 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