{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:17:02Z","timestamp":1788225422964,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["ICMR\/14\/1923\/SGP-2023 25\\u201326"],"award-info":[{"award-number":["ICMR\/14\/1923\/SGP-2023 25\\u201326"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["ICMRCAREP-2023-0000176"],"award-info":[{"award-number":["ICMRCAREP-2023-0000176"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["ICMR P521"],"award-info":[{"award-number":["ICMR P521"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.isci.2026.116635","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:59:14Z","timestamp":1782763154000},"page":"116635","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing the structural determinants amenable for polypharmacological behavior of 7D against Sirt1 and CXCR3"],"prefix":"10.1016","volume":"29","author":[{"given":"Kiran Bharat","family":"Lokhande","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhani Ram","family":"Mahato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra","family":"Asthana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.116635_bib1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1586\/ecp.12.74","article-title":"Polypharmacology: drug discovery for the future","volume":"6","author":"Reddy","year":"2013","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"10.1016\/j.isci.2026.116635_bib2","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/s44321-024-00137-8","article-title":"7D, a small molecule inhibits dengue infection by increasing interferons and neutralizing-antibodies via CXCL4:CXCR3:p38:IRF3 and Sirt1:STAT3 axes respectively","volume":"16","author":"Gaur","year":"2024","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.isci.2026.116635_bib3","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.3390\/v16121825","article-title":"Special Issue \u201cHost Targeted Therapeutics Against Virus Infections.\u201d","volume":"16","author":"Pleschka","year":"2024","journal-title":"Viruses"},{"key":"10.1016\/j.isci.2026.116635_bib4","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/j.chembiol.2024.10.009","article-title":"Host specific sphingomyelin is critical for replication of diverse RNA viruses","volume":"31","author":"Han","year":"2024","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.isci.2026.116635_bib5","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1021\/acs.jcim.0c01193","article-title":"Elucidation of Structural Determinants Delineates the Residues Playing Key Roles in Differential Dynamics and Selective Inhibition of Sirt1-3","volume":"61","author":"Singh","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.isci.2026.116635_bib6","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1039\/D1RA06149F","article-title":"Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors","volume":"12","author":"Purushotham","year":"2022","journal-title":"RSC Adv."},{"key":"10.1016\/j.isci.2026.116635_bib7","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","article-title":"The Sirtuin family in health and disease","volume":"7","author":"Wu","year":"2022","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.isci.2026.116635_bib8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.tem.2013.12.001","article-title":"SIRT1 and other Sirtuins in metabolism","volume":"25","author":"Chang","year":"2014","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.isci.2026.116635_bib9","doi-asserted-by":"crossref","DOI":"10.1172\/JCI158453","article-title":"Biological aging processes underlying cognitive decline and neurodegenerative disease","volume":"132","author":"Gonzales","year":"2022","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.isci.2026.116635_bib10","article-title":"Epigenetic Regulation Associated With Sirtuin 1 in Complications of Diabetes Mellitus","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.isci.2026.116635_bib11","article-title":"Regulation of SIRT1 and Its Roles in Inflammation","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.116635_bib12","doi-asserted-by":"crossref","first-page":"484","DOI":"10.7150\/ijbs.78654","article-title":"Novel Role of the SIRT1 in Endocrine and Metabolic Diseases","volume":"19","author":"Lu","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.isci.2026.116635_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115573","article-title":"Role of Sirtuins in hepatocellular carcinoma progression and multidrug resistance: Mechanistical and pharmacological perspectives","volume":"212","author":"Ceballos","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.isci.2026.116635_bib14","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.7150\/thno.100667","article-title":"Targeting Sirtuins for cancer therapy: epigenetics modifications and beyond","volume":"14","author":"Shen","year":"2024","journal-title":"Theranostics"},{"key":"10.1016\/j.isci.2026.116635_bib15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.pharmthera.2018.03.004","article-title":"Sirtuin activators and inhibitors: Promises, achievements, and challenges","volume":"188","author":"Dai","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.isci.2026.116635_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2020.144558","article-title":"Impact of structurally diverse BET inhibitors on SIRT1","volume":"741","author":"Tenhunen","year":"2020","journal-title":"Gene"},{"key":"10.1016\/j.isci.2026.116635_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.104768","article-title":"Discovery and characterization of small molecule SIRT3-specific inhibitors as revealed by mass spectrometry","volume":"110","author":"Loharch","year":"2021","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.isci.2026.116635_bib18","doi-asserted-by":"crossref","first-page":"7645","DOI":"10.1038\/ncomms8645","article-title":"Crystallographic structure of a small molecule SIRT1 activator-enzyme complex","volume":"6","author":"Dai","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2026.116635_bib19","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.3892\/ijo.2013.2035","article-title":"Discovery of a potent small molecule SIRT1\/2 inhibitor with anticancer effects","volume":"43","author":"Choi","year":"2013","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.isci.2026.116635_bib20","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1021\/acschembio.1c00331","article-title":"Pharmacological Advantage of SIRT2-Selective versus pan-SIRT1-3 Inhibitors","volume":"16","author":"Hong","year":"2021","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.isci.2026.116635_bib21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1128\/JVI.03220-14","article-title":"Intricate Roles of Mammalian Sirtuins in Defense against Viral Pathogens","volume":"90","author":"Budayeva","year":"2016","journal-title":"J. Virol."},{"key":"10.1016\/j.isci.2026.116635_bib22","doi-asserted-by":"crossref","DOI":"10.3390\/ph17101298","article-title":"Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity","volume":"17","author":"Shenk","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.isci.2026.116635_bib23","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nrm.2016.93","article-title":"Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds","volume":"17","author":"Bonkowski","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2026.116635_bib24","article-title":"SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases","volume":"11","author":"Manjula","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.isci.2026.116635_bib25","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1101\/gad.265462.115","article-title":"Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol","volume":"29","author":"Cao","year":"2015","journal-title":"Genes Dev."},{"key":"10.1016\/j.isci.2026.116635_bib26","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s10753-015-0276-0","article-title":"CXCR3 May Help Regulate the Inflammatory Response in Acute Lung Injury via a Pathway Modulated by IL-10 Secreted by CD8 + CD122+ Regulatory T Cells","volume":"39","author":"Nie","year":"2016","journal-title":"Inflammation"},{"key":"10.1016\/j.isci.2026.116635_bib27","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.yexcr.2010.12.017","article-title":"CXCR3 in T cell function","volume":"317","author":"Groom","year":"2011","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.isci.2026.116635_bib28","doi-asserted-by":"crossref","first-page":"30219","DOI":"10.1074\/jbc.M403595200","article-title":"Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function","volume":"279","author":"Colvin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.116635_bib29","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1749-6632.2009.04813.x","article-title":"CXCR3, inflammation, and autoimmune diseases","volume":"1173","author":"Lacotte","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.isci.2026.116635_bib30","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1038\/s41598-021-82167-7","article-title":"Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation","volume":"11","author":"Hasegawa","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.isci.2026.116635_bib31","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1600-6143.2011.03859.x","article-title":"CXCR3 chemokine ligands during respiratory viral infections predict lung allograft dysfunction","volume":"12","author":"Weigt","year":"2012","journal-title":"Am. J. Transplant"},{"key":"10.1016\/j.isci.2026.116635_bib32","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.humimm.2015.03.019","article-title":"Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia","volume":"76","author":"Hoh","year":"2015","journal-title":"Hum. Immunol."},{"key":"10.1016\/j.isci.2026.116635_bib33","doi-asserted-by":"crossref","DOI":"10.1590\/0037-8682-0128-2023","article-title":"The CXCL9\/10\/11-CXCR3 axis as a predictor of COVID-19 progression: a prospective, case-control study","volume":"56","author":"\u00c7elik","year":"2023","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"10.1016\/j.isci.2026.116635_bib34","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.apsb.2025.03.011","article-title":"Overview of host-directed antiviral targets for future research and drug development","volume":"15","author":"Gu","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.isci.2026.116635_bib35","doi-asserted-by":"crossref","first-page":"6150","DOI":"10.1021\/acs.jpcb.9b01859","article-title":"Conformational Characterization of Linker Revealed the Mechanism of Cavity Formation by 227G in BVDV RDRP","volume":"123","author":"Mittal","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.isci.2026.116635_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.abb.2021.109059","article-title":"Targeting cryptic-orthosteric site of PD-L1 for inhibitor identification using structure-guided approach","volume":"713","author":"Mittal","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.isci.2026.116635_bib37","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.isci.2026.116635_bib38","series-title":"AMBER 22 Reference Manual","author":"Case","year":"2022"},{"key":"10.1016\/j.isci.2026.116635_bib39","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.isci.2026.116635_bib40","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1063\/1.1590311","article-title":"Free energy calculation from steered molecular dynamics simulations using Jarzynski\u2019s equality","volume":"119","author":"Park","year":"2003","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.isci.2026.116635_bib41","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/jcc.540161104","article-title":"Multidimensional free-energy calculations using the weighted histogram analysis method","volume":"16","author":"Kumar","year":"1995","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.isci.2026.116635_bib42","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1021\/acs.jcim.9b00843","article-title":"Exploring Ligand Stability in Protein Crystal Structures Using Binding Pose Metadynamics","volume":"60","author":"Fusani","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.isci.2026.116635_bib43","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1021\/acs.jcim.9b01118","article-title":"Impact of Different Automated Binding Pose Generation Approaches on Relative Binding Free Energy Simulations","volume":"60","author":"Cappel","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.isci.2026.116635_bib44","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1080\/07391102.2020.1835722","article-title":"Development of potential proteasome inhibitors against Mycobacterium tuberculosis","volume":"40","author":"Tyagi","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.isci.2026.116635_bib45","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.isci.2026.116635_bib46","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10822-006-9087-6","article-title":"PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodol","volume":"20","author":"Dixon","year":"2006","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.isci.2026.116635_bib47","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.639614","article-title":"Molecular Dynamics Simulations Reveal the Interaction Fingerprint of Remdesivir Triphosphate Pivotal in Allosteric Regulation of SARS-CoV-2 RdRp","volume":"8","author":"Srivastava","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.isci.2026.116635_bib48","doi-asserted-by":"crossref","first-page":"9287","DOI":"10.1080\/07391102.2021.1927844","article-title":"Binding mode characterization of 13b in the monomeric and dimeric states of SARS-CoV-2 main protease using molecular dynamics simulations","volume":"40","author":"Kumari","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.isci.2026.116635_bib49","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.658312","article-title":"Conformational Characterization of the Co-Activator Binding Site Revealed the Mechanism to Achieve the Bioactive State of FXR","volume":"8","author":"Kumari","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.isci.2026.116635_bib50","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1002\/pro.4398","article-title":"Characterizing (un)binding mechanism of USP7 inhibitors to unravel the cause of enhanced binding potencies at allosteric checkpoint","volume":"31","author":"Srivastava","year":"2022","journal-title":"Protein Sci."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226020110?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226020110?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:11:34Z","timestamp":1788225094000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226020110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["S2589004226020110"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.116635","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Harnessing the structural determinants amenable for polypharmacological behavior of 7D against Sirt1 and CXCR3","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.116635","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"116635"}}