{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:06:42Z","timestamp":1778843202379,"version":"3.51.4"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2026,5,11]]},"abstract":"\n Objective:<\/jats:title>\n To elucidate potential molecular intersections between ribavirin\nand Major Depressive Disorder (MDD) and to generate testable hypotheses regarding\nneuropsychiatric safety and mechanism of action.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Ribavirin-associated targets were integrated from Swiss Target Prediction,\nTargetNet, and SuperPred (n = 163), and MDD-related genes were compiled from\nOMIM and GeneCards (n = 2035). Venn analysis identified 45 overlapping candidates.\nA STRING-based protein interaction network was analyzed in Cytoscape using CytoNCA\nto prioritize core targets. Functional interpretation included GO and KEGG enrichment\nvia OmicShare, cell type annotation with PanglaoDB, molecular docking, and transcriptomic\ncross-validation using the GSE76826 peripheral blood dataset.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Five core targets emerged as central nodes, namely CCND1, SIRT1, NFKB1,\nEP300, and MAPK1, each linked to neurogenesis, synaptic plasticity, immune and inflammatory\nregulation, epigenetic control, and stress signaling. Enrichment analyses\nhighlighted processes and pathways relevant to MDD, including responses to oxygencontaining\ncompounds, cell death, HIF-1 signaling, neurotrophin signaling, cellular senescence,\nand ferroptosis. Cell type annotations associated core targets with fibroblasts,\ndendritic cells, natural killer cells, and neurons. Docking suggested plausible hydrogen-\nbonded interactions between ribavirin and core proteins. Cross-validation with\nGSE76826 supported overlap with differentially expressed genes, pathway concordance,\nand altered expression of select core targets in MDD compared with controls.<\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n The convergence of targets and pathways with established MDD biology\nsupports the plausibility that ribavirin intersects depression-relevant mechanisms. Limitations\ninclude reliance on curated databases, potential hub bias in network topology, limited\ntissue and cell-type specificity in enrichment, the approximate nature of docking, uncertain\nbrain exposure at clinical doses, and tissue mismatch when using peripheral\nblood for validation. Clinical attribution is further complicated by co-therapy, underlying\ninfection, and psychosocial factors. These findings are hypothesis-generating and\nshould guide targeted experimental and clinical validation.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Ribavirin may engage key axes of MDD biology through core targets such\nas CCND1, SIRT1, NFKB1, EP300, and MAPK1. The results support risk assessment\nand focused monitoring of depressive symptoms in ribavirin-treated patients and outline\npriorities for mechanistic validation.<\/jats:p>\n <\/jats:sec>","DOI":"10.2174\/0109298673418108260303083054","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:06:58Z","timestamp":1778839618000},"update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Insights into Ribavirin\u2019s Potential Impact on Major Depressive Disorder: A Network Toxicology Study"],"prefix":"10.2174","volume":"33","author":[{"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine Psychosis, Suzhou Guangji Hospital, Suzhou, 215131, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiancheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cancan","family":"Fang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Key Laboratory of Xin'an Medicine, the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Key Laboratory of Xin'an Medicine, the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Shen","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Key Laboratory of Xin'an Medicine, the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Key Laboratory of Xin'an Medicine, the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","container-title":["Current Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0109298673418108260303083054","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/253813\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0109298673418108260303083054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:07:10Z","timestamp":1778839630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/253813\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":0,"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0109298673418108260303083054","relation":{},"ISSN":["0929-8673"],"issn-type":[{"value":"0929-8673","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2025-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-24","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}