{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:13:14Z","timestamp":1777972394939,"version":"3.51.4"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Kaposi\u2019s sarcoma (KS) is an angioproliferative malignancy caused by Kaposi\u2019s sarcoma-associated herpesvirus (KSHV), characterized by aberrant angiogenesis, chronic inflammation, and endothelial cell transformation. Given the multi-factorial nature of KS pathogenesis, strategies that simultaneously modulate multiple mo-lecular targets are considered more promising than single-target approaches. However, effective multi-target therapeutic agents for KS remain limited, prompting this study to employ an integrative in silico pipeline. Methods: An integrative in silico pipeline combining compound screening, target predic-tion, network pharmacology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Ge-nomes (KEGG) enrichment, protein\u2013protein interaction (PPI) analysis, molecular docking, and molecular dynamics (MD) simulations was employed. Streptomyces-derived metabolites were prioritized based on chemical diversity, annotation, and clinical prece-dent. Predicted targets were intersected with KS-associated genes, with hubs ranked by network topology. Docking and MD simulations evaluated binding affinity and stability. Results: Endostemonine I emerged as the top candidate, engaging nine of ten hub proteins, including EGFR, mTOR, PTGS2, SRC, PARP1, PPAR\u03b3, MAPK1, MAPK14, and ICAM1. Key nodes such as mTOR, PTGS2, PPAR\u03b3, and MAPK14 are central to KS-related an-gi-ogenesis, inflammation, and viral oncogenesis. GO and KEGG analyses revealed en-richment in kinase activity, cell adhesion, and PI3K\u2013Akt\/mTOR and MAPK signaling pathways. Docking indicated strong binding to mTOR, PTGS2, PARP1, PPAR\u03b3, and MAPK14, while MD simulations confirmed stable interactions for mTOR, PTGS2, PPAR\u03b3, and MAPK14. Conclusions: Collectively, these proteins represent high-confidence, druggable KS targets, with Endostemonine I as a promising multi-target scaffold. These findings highlight the therapeutic potential of Endostemonine I and warrant further validation through future in vitro and in vivo studies.<\/jats:p>","DOI":"10.3390\/medsci14020237","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:57:29Z","timestamp":1777967849000},"page":"237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endostemonine I as a Multi-Target Inhibitor of Kaposi\u2019s Sarcoma-Associated Herpesvirus Oncogenic Pathways: An Integrative Computational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-5311","authenticated-orcid":false,"given":"Imran","family":"Sama-ae","sequence":"first","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"},{"name":"Center of Excellence Research for Melioidosis and Microorganisms (CERMM), Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mollaya","family":"Daloh","sequence":"additional","affiliation":[{"name":"Kapho Hospital, Kapho District, Pattani 94230, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aman","family":"Tedasen","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-4333","authenticated-orcid":false,"given":"Siriruk","family":"Changrob","sequence":"additional","affiliation":[{"name":"Drukier Institute for Children\u2019s Health, Weill Cornell Medicine, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monthon","family":"Lertcanawanichakul","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-801X","authenticated-orcid":false,"given":"Pattamaporn","family":"Kwankaew","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phenphitcha","family":"Issaro","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natthanicha","family":"Maidam","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nichakan","family":"Rattanapong","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurul","family":"Auma","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirfart","family":"Kaseng","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3088-7055","authenticated-orcid":false,"given":"Malatee","family":"Tayeh","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala District, Nakhon Si Thammarat 80160, Thailand"},{"name":"Hematology and Transfusion Science Research Center 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