{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:19:19Z","timestamp":1785417559351,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["ORF-2026-984"],"award-info":[{"award-number":["ORF-2026-984"]}]},{"award":["ORF-2026-984"],"award-info":[{"award-number":["ORF-2026-984"]}],"id":[{"id":"https:\/\/ror.org\/02f81g417","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>West Nile virus (WNV) is a mosquito-borne pathogen of escalating epidemiological importance and a growing global health concern, driven by the climate-associated expansion of its Culex mosquito vectors. Although WNV is an extensively studied flavivirus, most host\u2013pathogen interaction studies focus on static and structural aspects rather than dynamic and functional ones. Delineating phosphorylation-mediated interactions between WNV proteins and human kinases bridges a critical gap by providing important insight into the molecular mechanisms underlying infection. In this study, we investigated potential phosphorylation-mediated interactions between WNV proteins and human kinases using an integrative computational framework combining motif prediction, phosphoproteomic data analysis and structural docking. Key interactions were predicted between viral proteins and regulatory kinases within the AKT-ERK pathway and the AMPK-mediated autophagy, including major network kinases such as RAF1, IKBKB, and ULK1. In addition, experimentally validated phosphorylation sites in viral proteins were found to be associated with multiple candidate host kinases, including MAP2K7 and MAP2K9, suggesting complex regulatory networks. Integration with phosphoproteomic datasets supported the relevance of multiple predicted kinases, including those associated with antiviral responses and translational regulation. Protein\u2013protein docking demonstrated stable, energetically favorable interactions between selected host kinases and viral proteins, particularly the viral polymerase (NS5), helicase (NS3), and NS1. The findings of this study establish a framework for future research on the development of host-directed antiviral strategies.<\/jats:p>","DOI":"10.3390\/v18080825","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Potential Human Kinase-Viral Substrate Network of West Nile Virus"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3710-5879","authenticated-orcid":false,"given":"Akash","family":"Anil","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayisha A.","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineetha","family":"Shaji","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-6312","authenticated-orcid":false,"given":"Mukhtar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8273-0687","authenticated-orcid":false,"given":"Bristow Ben","family":"Joseph","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aromal Monipillil","family":"Ajayakumar","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-3379","authenticated-orcid":false,"given":"Prashant Kumar","family":"Modi","sequence":"additional","affiliation":[{"name":"Center for Systems Biology and Molecular Medicine (CSBMM), Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6732-4486","authenticated-orcid":false,"given":"Abhithaj","family":"Jayanandan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya","family":"Soman","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashwanth","family":"Subbannayya","sequence":"additional","affiliation":[{"name":"School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-121X","authenticated-orcid":false,"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5501\/wjv.v1.i2.51","article-title":"West Nile Virus: A Re-Emerging Pathogen Revisited","volume":"1","author":"Saiz","year":"2012","journal-title":"World J. 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