Potential targetability of Leishmania donovani proteins to anti-retroviral Amprenavir and Darunavir: an in silico drug repurposing analysis

Potential targetability of Leishmania donovani proteins to anti-retroviral Amprenavir and Darunavir: an in silico drug repurposing analysis | 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 Potential targetability of Leishmania donovani proteins to anti-retroviral Amprenavir and Darunavir: an in silico drug repurposing analysis Umesh Chandra Halder This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8671159/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 Lethal Kala-azar, or visceral leishmaniasis, is the infective outcome of intracellular Leishmania donovani to its sole reservoir, the humans, mainly in the tropics, with an annual mortality of ~ 50,000. To date, the treatment regimen includes antimony compounds, miltefosine, amphotericin B, and paramomycin with region-specific effectiveness and mild to severe life-threatening side effects like cardiotoxicity, nephrotoxicity, pancreatitis, myocarditis, and ototoxicity. To solve these harms, alternative drugs have been proposed through computational biology and drug repurposing. In the present study, protein-drug docking analyses of forty-five proteins were performed comparing the structurally similar amino acid side chains in their 3D-crystal structures using SPRITE and ASSAM. Further, to validate the effectiveness of the predicted drugs, their association with the conserved active sites of thirty leishmanial enzymes was studied using GASS. Results delivered two known potent anti-HIV drugs, viz., Amprenavir and Darunavir. These two drugs targeted almost all the candidate proteins with maximum unique binding interfaces. Hence, therapeutic treatments with a combination of these two may effectively intervene with L. donovani proteins and eventually its life cycle. Biological sciences/Biochemistry Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Kala-azar Drug repurposing Amprenavir Darunavir Docking Leishmania donovani Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFiguresandTables.pdf 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. 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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-8671159","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":586435837,"identity":"7461f5e0-714f-4990-aada-3806ba357e1f","order_by":0,"name":"Umesh Chandra Halder","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIie3PsUrDQBjA8SsHl+VLXU/O6itUArFQxVdpKNx0QR8gSKdOJV3rW2QqOCkcxiWzBOIigQhOwkEXofil80XaTeT+Q/LluB93IcTl+qNRQp7wNWmHUW9GaPvFT/YlHAmbtAQOITBsVzvJ8FVrc5u8nV148TsOfLAUhfkskxEQTz9nNlJJKVZ5c/6w+Ahw4MF9Gq/HKseLgZSllaiQ+jPdy0pJBDAeZYW/DhRDwiG0kxtjkFwjod+w5dFjAU2gtr8RRQSSCAkT/hxPAaB1PO8mx5UMBeR6mhUNG/spD1YFC2mccmAd/9KvprWBRF9lL5JWsLkcLBe0Nmpzd3rk6dxGrDG+e+67vY1+HbLb5XK5/n0/EyNlQql0S1QAAAAASUVORK5CYII=","orcid":"","institution":"Raniganj Girls' College","correspondingAuthor":true,"prefix":"","firstName":"Umesh","middleName":"Chandra","lastName":"Halder","suffix":""}],"badges":[],"createdAt":"2026-01-22 14:55:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8671159/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8671159/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104400054,"identity":"df8712c5-6bca-4b3a-bbb7-b5337ec2e3ce","added_by":"auto","created_at":"2026-03-11 12:08:42","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11796413,"visible":true,"origin":"","legend":"","description":"","filename":"Leishmaniamanuscript2026R.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8671159/v1_covered_a076a8df-01c0-46a6-a598-e8c64fc8c2a6.pdf"},{"id":102222549,"identity":"6d9df27e-45f6-4867-af15-f831b2ac4fbd","added_by":"auto","created_at":"2026-02-09 14:07:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":3738626,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFiguresandTables.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8671159/v1/50b78fa6dad4ccc940537eac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Potential targetability of Leishmania donovani proteins to anti-retroviral Amprenavir and Darunavir: an in silico drug repurposing analysis ","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":"Kala-azar, Drug repurposing, Amprenavir, Darunavir, Docking, Leishmania donovani","lastPublishedDoi":"10.21203/rs.3.rs-8671159/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8671159/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLethal Kala-azar, or visceral leishmaniasis, is the infective outcome of intracellular \u003cem\u003eLeishmania donovani\u003c/em\u003e to its sole reservoir, the humans, mainly in the tropics, with an annual mortality of ~\u0026thinsp;50,000. To date, the treatment regimen includes antimony compounds, miltefosine, amphotericin B, and paramomycin with region-specific effectiveness and mild to severe life-threatening side effects like cardiotoxicity, nephrotoxicity, pancreatitis, myocarditis, and ototoxicity. To solve these harms, alternative drugs have been proposed through computational biology and drug repurposing. In the present study, protein-drug docking analyses of forty-five proteins were performed comparing the structurally similar amino acid side chains in their 3D-crystal structures using SPRITE and ASSAM. Further, to validate the effectiveness of the predicted drugs, their association with the conserved active sites of thirty leishmanial enzymes was studied using GASS. Results delivered two known potent anti-HIV drugs, viz., Amprenavir and Darunavir. These two drugs targeted almost all the candidate proteins with maximum unique binding interfaces. 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