Triterpene esters from Uncaria rhynchophylla hooks are able as new selective inhibitors on HIV-1 protease and their molecular docking study

Triterpene esters from Uncaria rhynchophylla hooks are able as new selective inhibitors on HIV-1 protease and their molecular docking 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 Article Triterpene esters from Uncaria rhynchophylla hooks are able as new selective inhibitors on HIV-1 protease and their molecular docking study JiSuk Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4738272/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Dec, 2024 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Despite the remarkable advancements achieved with combination anti-retroviral agents (cART), the complete eradication of Human immunodeficiency virus (HIV) remains a formidable challenge due to various factors including adverse effects, adherence issues, and the emergence of viral resistance to existing therapies. Consequently, there is an urgent need for the development of safer and more effective drugs to combat modern resistant viral strains and advance acquired immunodeficiency syndrome (AIDS) therapeutics. Eight triterpene esters (1–8) were identified from Uncaria rhynchophylla hooks. These compounds exhibited selective inhibition of HIV-1 protease, with 3β-hydroxy-27-p-Z-coumaroyloxyurs-12-en-28-oic acid (8), showing the most potent inhibitory activity. Structure-activity relationship analysis highlighted the importance of an ursane moiety, a cis configuration, and a p-coumaroyloxy group for inhibitory activity. In silico docking results elucidate specific amino acid residues Asp29B, Lys45B, and Asn25A, interacting with the aromatic hydroxyl group at 7′, and carboxylic acid at 28. In addition, it interacts via π/anion and π/alkyl and alkyl hydrophobic interactions responsible for interactions and their mode of action. The study suggests that triterpene esters from U. rhynchophylla could represent a new class of selective HIV-1 protease inhibitors with less toxicity, suitable for combination antiretroviral therapy for AIDS. Biological sciences/Chemical biology/Enzyme mechanisms Biological sciences/Drug discovery/Pharmaceutics Uncaria rhynchophylla triterpene ester selective HIV-1 protease inhibitor Structure-activity relationship molecular docking study Full Text Additional Declarations No competing interests reported. Supplementary Files JSLEETESciRepsupp1240717.docx Cite Share Download PDF Status: Published Journal Publication published 30 Dec, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 20 Aug, 2024 Reviews received at journal 18 Aug, 2024 Reviews received at journal 09 Aug, 2024 Reviewers agreed at journal 28 Jul, 2024 Reviewers agreed at journal 28 Jul, 2024 Reviewers agreed at journal 28 Jul, 2024 Reviewers invited by journal 27 Jul, 2024 Editor assigned by journal 27 Jul, 2024 Editor invited by journal 27 Jul, 2024 Submission checks completed at journal 25 Jul, 2024 First submitted to journal 14 Jul, 2024 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-4738272","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":342938156,"identity":"622f77b3-0921-4bee-ba27-4cad2d4d8349","order_by":0,"name":"JiSuk Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIie3RMQrCMBiG4S8UnIquKQW9QopQHErP0hLoJOIBHCJCXcSsgpcQvEBKoVPFtaNH6CSCIsZBcDIdHfJuCXlIfgLYbH8YEY4AGI0Hnx1qJkSTecQ90ZW8EdBm5KC6EkcWy0vLSmd8PlUUixjeXv0mZJeugh0r+2EzyygqDr+fmAjJfVffEjZuSNFTGLqmSWSxvj9YSY6y1uTZhYg0d8D0+JiGlOQKvpHoWbwNizhtpuNJuuWutzGQQJZFe3vor5R10LTXeEhrExHfqwQwPQsYGU/YbDab7QVs2j3AI93ofAAAAABJRU5ErkJggg==","orcid":"","institution":"College of Pharmacy, Seoul National University","correspondingAuthor":true,"prefix":"","firstName":"JiSuk","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-07-14 12:00:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4738272/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4738272/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-76551-2","type":"published","date":"2024-12-30T15:57:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":73095101,"identity":"913c5ecb-2aa7-4234-83b6-a4fab58dade8","added_by":"auto","created_at":"2025-01-06 16:24:41","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2167314,"visible":true,"origin":"","legend":"","description":"","filename":"JSLEETESciRepmain240725.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4738272/v1_covered_67d6de91-194e-423e-97a5-07d47a1f956d.pdf"},{"id":62949480,"identity":"7f85e3bb-b661-4cc4-be02-0652a100109f","added_by":"auto","created_at":"2024-08-21 11:00:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":44692,"visible":true,"origin":"","legend":"","description":"","filename":"JSLEETESciRepsupp1240717.docx","url":"https://assets-eu.researchsquare.com/files/rs-4738272/v1/49b58e62b9849a456a3e9261.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Triterpene esters from Uncaria rhynchophylla hooks are able as new selective inhibitors on HIV-1 protease and their molecular docking study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"Uncaria rhynchophylla, triterpene ester, selective HIV-1 protease inhibitor, Structure-activity relationship, molecular docking study","lastPublishedDoi":"10.21203/rs.3.rs-4738272/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4738272/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite the remarkable advancements achieved with combination anti-retroviral agents (cART), the complete eradication of Human immunodeficiency virus (HIV) remains a formidable challenge due to various factors including adverse effects, adherence issues, and the emergence of viral resistance to existing therapies. 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