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However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1\u00a0F and HSV-1\/153 (a clinical drug-resistant strain) replication, with an EC<jats:sub>50<\/jats:sub> of 9.34 \u00b5M and 5.84 \u00b5M, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1\/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.<\/jats:p>","DOI":"10.1186\/s12985-024-02384-0","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T19:01:44Z","timestamp":1716836504000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Harmol used for the treatment of herpes simplex virus induced keratitis"],"prefix":"10.1186","volume":"21","author":[{"given":"Huanhuan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"issue":"4","key":"2384_CR1","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.3892\/or.2013.2242","volume":"29","author":"A Abe","year":"2013","unstructured":"Abe A, Kokuba H. Harmol induces autophagy and subsequent apoptosis in U251MG human glioma cells through the downregulation of survivin. Oncol Rep. 2013;29(4):1333\u201342. https:\/\/doi.org\/10.3892\/or.2013.2242.","journal-title":"Oncol Rep"},{"issue":"5","key":"2384_CR2","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1097\/CAD.0b013e32832a2dd9","volume":"20","author":"A Abe","year":"2009","unstructured":"Abe A, Yamada H. Harmol induces apoptosis by caspase-8 activation independently of Fas\/Fas ligand interaction in human lung carcinoma H596 cells. Anticancer Drugs. 2009;20(5):373\u201381. https:\/\/doi.org\/10.1097\/CAD.0b013e32832a2dd9.","journal-title":"Anticancer Drugs"},{"issue":"12","key":"2384_CR3","doi-asserted-by":"publisher","first-page":"4371","DOI":"10.1002\/fsn3.3031","volume":"10","author":"G Abulimiti","year":"2022","unstructured":"Abulimiti G, Zeng J, Aimaiti M, Lei X, Mi N. 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