{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:36:50Z","timestamp":1788219410345,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2024C03206"],"award-info":[{"award-number":["2024C03206"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171021"],"award-info":[{"award-number":["82171021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Herpes simplex keratitis (HSK) is a leading infectious cause of blindness worldwide, with current therapies primarily targeting viral replication rather than addressing host\u2010cell injury. RNA sequencing of corneal tissue from HSK patients and healthy donors identifies a metabolic shift from mitochondrial oxidative phosphorylation to aerobic glycolysis. Notably, hexokinase\u20102 (HK2), a pivotal glycolytic enzyme, exhibits the greatest up\u2010regulation, coinciding with a marked reduction in the activity of mitochondrial respiratory chain complexes in HSK corneas. Pharmacological inhibition of HK2 with lonidamine in human corneal epithelial cells reduces herpes simplex virus type 1 (HSV\u20101) replication while preserving cell viability. In a murine model of HSK, topical lonidamine restored respiratory\u2010chain activity, lowered viral load, and accelerated corneal re\u2010epithelialization; its early therapeutic efficacy surpassed that of ganciclovir, and combination therapy conferred additive benefit. These findings identify HK2\u2010driven glycolytic reprogramming as a pathogenic hallmark of HSK and demonstrate that metabolic targeting concurrently restricts viral propagation and promotes tissue regeneration. Thus, metabolic intervention has the potential to complement direct antiviral therapy and represents a promising, clinically translatable strategy to preserve vision in HSK.<\/jats:p>","DOI":"10.1002\/advs.202503690","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T09:33:59Z","timestamp":1750412039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hexokinase\u20102 as a Therapeutic Target: Alleviating Herpes Simplex Keratitis Through Metabolic Reprogramming"],"prefix":"10.1002","volume":"12","author":[{"given":"Dan","family":"Jiang","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Ocular Diseases Eye Hospital Wenzhou Medical University  Wenzhou 325000 China"},{"name":"State Key Laboratory of Ophthalmology Optometry and Visual Science Eye Hospital Wenzhou Medical University  Wenzhou 325000 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