Antibacterial potential of hippophaenin-A against foodborne pathogens: a comprehensive in silico study

Antibacterial potential of hippophaenin-A against foodborne pathogens: a comprehensive in silico study | 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 Research Article Antibacterial potential of hippophaenin-A against foodborne pathogens: a comprehensive in silico study Padmika Madushanka Wadanambi, Kapila Seneviratne, Nimanthi Jayathilaka This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6150888/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Bacteria are a major cause of foodborne illnesses. Natural compounds with antimicrobial properties, such as tannins, can inhibit bacterial growth and enhance food safety. Peptidoglycan, a key component of the bacterial cell wall, is essential for bacterial growth, making penicillin-binding proteins (PBPs) in its peptidoglycan synthesis pathway a promising target for antibacterial strategies. Hippophaenin-A, a tannin from Hippophae rhamnoides L. (sea buckthorn), was analyzed through computer simulations to investigate its inhibitory effects on eight PBPs from Staphylococcus aureus , Bacillus cereus , Escherichia coli , and Salmonella typhimurium . Phylogenetic analysis of PBP sequences was conducted using MEGA 11.0. 3D models of PBPs were obtained from the AlphaFold2 Protein Structure Database and validated. Molecular docking with AutoDock Vina assessed the binding affinity and interactions of hippophaenin-A and chloramphenicol in PBP active sites. Molecular dynamics simulations (50 ns) were performed for top docking complexes and native PBPs of foodborne pathogens. Physicochemical, pharmacokinetic, and toxicity (ADME/T) properties of hippophaenin-A were also evaluated. Hippophaenin-A e binding affinities of -9.4, and − 9.3 kcal/mol with the transpeptidase and transglycosylase catalytic sites of Salmonella typhimurium PBP1B, and Bacillus cereus PBP3, respectively, surpassing the positive control. These findings suggest its antibacterial activity may result from PBP inhibition. Additionally, it displayed favorable physicochemical and ADME properties, with toxicity predictions indicating no safety concerns for consumers. Further studies on hippophaenin-A could provide valuable insights for developing it as a natural antibacterial agent for food preservation. Foodborne pathogens hippophaenin-A molecular dynamics penicillin binding proteins Staphylococcus aureus tannins Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-6150888","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":443757957,"identity":"08d08398-8977-4efa-8459-b2a17c8eb11b","order_by":0,"name":"Padmika Madushanka Wadanambi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYJACCRBhwMx8AMSWIUULWwKIzUOCFgYeAxBNWIu5RPLDGz932EWbs/N8fnWjxoKHgf3w0Q34tFjOSDO27D2TnLuzmXebdc4xoMN40tJu4NNicDvBTIK3jTl3w2HebcY5bEAtEjxmBLSkf5P821YP1MLzzDjnH1FacsykedsOg7QwP85tI0KL5fw3xdaybceBfmEzY87tk+BhI+QXc57jG2++bavO3c5/+PHnnG91cvzsh4/hdxgSmw0cQWz4lKNrYf5ASPUoGAWjYBSMTAAAIyZGqCEVMTsAAAAASUVORK5CYII=","orcid":"","institution":"University of Kelaniya","correspondingAuthor":true,"prefix":"","firstName":"Padmika","middleName":"Madushanka","lastName":"Wadanambi","suffix":""},{"id":443757958,"identity":"e9cf2cd1-0e2f-498b-9d45-1d002f44c95b","order_by":1,"name":"Kapila Seneviratne","email":"","orcid":"","institution":"University of Kelaniya","correspondingAuthor":false,"prefix":"","firstName":"Kapila","middleName":"","lastName":"Seneviratne","suffix":""},{"id":443757959,"identity":"1f96529e-ee31-4ecc-8de7-85defd460ae0","order_by":2,"name":"Nimanthi Jayathilaka","email":"","orcid":"","institution":"University of Kelaniya","correspondingAuthor":false,"prefix":"","firstName":"Nimanthi","middleName":"","lastName":"Jayathilaka","suffix":""}],"badges":[],"createdAt":"2025-03-04 05:08:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6150888/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6150888/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84979353,"identity":"4ad33831-005e-401c-a0e7-c5765404febe","added_by":"auto","created_at":"2025-06-19 13:01:22","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3502063,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptAmended.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6150888/v1_covered_5e64a829-3d75-44cf-9b63-e97841529871.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibacterial potential of hippophaenin-A against foodborne pathogens: a comprehensive in silico study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Foodborne pathogens, hippophaenin-A, molecular dynamics, penicillin binding proteins, Staphylococcus aureus, tannins","lastPublishedDoi":"10.21203/rs.3.rs-6150888/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6150888/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBacteria are a major cause of foodborne illnesses. Natural compounds with antimicrobial properties, such as tannins, can inhibit bacterial growth and enhance food safety. Peptidoglycan, a key component of the bacterial cell wall, is essential for bacterial growth, making penicillin-binding proteins (PBPs) in its peptidoglycan synthesis pathway a promising target for antibacterial strategies. Hippophaenin-A, a tannin from \u003cem\u003eHippophae rhamnoides\u003c/em\u003e L. (sea buckthorn), was analyzed through computer simulations to investigate its inhibitory effects on eight PBPs from \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eBacillus cereus\u003c/em\u003e, \u003cem\u003eEscherichia coli\u003c/em\u003e, and \u003cem\u003eSalmonella typhimurium\u003c/em\u003e. Phylogenetic analysis of PBP sequences was conducted using MEGA 11.0. 3D models of PBPs were obtained from the AlphaFold2 Protein Structure Database and validated. Molecular docking with AutoDock Vina assessed the binding affinity and interactions of hippophaenin-A and chloramphenicol in PBP active sites. Molecular dynamics simulations (50 ns) were performed for top docking complexes and native PBPs of foodborne pathogens. Physicochemical, pharmacokinetic, and toxicity (ADME/T) properties of hippophaenin-A were also evaluated. Hippophaenin-A e binding affinities of -9.4, and \u0026minus;\u0026thinsp;9.3 kcal/mol with the transpeptidase and transglycosylase catalytic sites of \u003cem\u003eSalmonella typhimurium\u003c/em\u003e PBP1B, and \u003cem\u003eBacillus cereus\u003c/em\u003e PBP3, respectively, surpassing the positive control. These findings suggest its antibacterial activity may result from PBP inhibition. Additionally, it displayed favorable physicochemical and ADME properties, with toxicity predictions indicating no safety concerns for consumers. 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