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Intrinsically disordered proteins and regions are key contributors to protein\u2013protein interaction networks due to their conformational flexibility and associated with it multifunctionality, binding promiscuity, and regulatory versatility. In this study, we performed a systematic, proteome\u2010wide analysis of intrinsic disorder in human proteins interacting with SARS\u2010CoV\u20102 by integrating five experimentally validated interaction datasets comprising 2055 unique host proteins. Using disorder prediction, structural confidence assessment, functional and domain annotation, protein\u2013protein interaction network analysis, phase\u2010separation propensity estimation, and independent validation with the D\n                    <jats:sup>2<\/jats:sup>\n                    P\n                    <jats:sup>2<\/jats:sup>\n                    platform on a selected set of proteins, we characterized the structural organization of the SARS\u2010CoV\u20102 human interactome. Our results reveal a balanced distribution of ordered and disordered host proteins, distinct functional and domain signatures across disorder classes, consistent inverse relationships between disorder and structural confidence, and increased network connectivity and phase\u2010separation propensity among highly disordered interactors. These findings indicate that SARS\u2010CoV\u20102 exploits structural diversity within the host proteome rather than preferentially targeting a single disorder class and highlight intrinsic disorder as a key contributor to interaction plasticity and network organization at the systems level.\n                  <\/jats:p>","DOI":"10.1002\/jcb.70098","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:00:55Z","timestamp":1781503255000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic Disorder Status in Human Proteins Interacting With SARS\u2010CoV\u20102 Proteins: Insights From Five Years of Translational Research"],"prefix":"10.1002","volume":"127","author":[{"given":"Muhamed","family":"Adilovi\u0107","sequence":"first","affiliation":[{"name":"Genetics and Bioengineering Study Program, Faculty of Engineering and Natural Sciences International University of Sarajevo  Sarajevo Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Akcesme","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Hamidiye Faculty of Medicine University of Health Sciences  \u00dcsk\u00fcdar\/\u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altijana","family":"Hromi\u0107\u2010Jahjefendi\u0107","sequence":"additional","affiliation":[{"name":"Genetics and Bioengineering Study Program, Faculty of Engineering and Natural Sciences International University of Sarajevo  Sarajevo Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020532"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.10.008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100887"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.02.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3110"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2012.675145"},{"key":"e_1_2_10_8_1","first-page":"473","article-title":"Protein Disorder and the Evolution of Molecular Recognition: Theory, Predictions and Observations","volume":"3","author":"Dunker A. 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