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Although 147B3 exhibits cytotoxicity, it inhibits the function of infected cell protein 4 (ICP4), a viral transcription factor essential for HSV\u20101 replication. In this study, we evaluated five commercially available compounds (1C6, 1C6L, 1H6, 1H6L, and 2D10) that had structural similarity to 147B3, exhibited potent anti\u2010HSV\u20101 activity with reduced cytotoxicity. Among these, 1C6L and 1H6L are structural analogs of 1C6 and 1H6, respectively. An HSV\u20101 strain resistant to 147B3 carrying a mutation in ICP4 exhibited resistance to all the five compounds, suggesting a shared mechanism of action involving ICP4. Among these compounds, 1H6L had the highest selective index against HSV\u20101. Notably, these compounds did not reduce early or late protein expression of HSV\u20101, unlike the parent compound 147B3. Although viral genome replication occurred in the presence of 1H6L, it prevented virion release into the culture supernatant. The cell fraction analysis revealed that 1H6L reduced the size of the cytoplasmic HSV\u20101 genome. These findings suggest that 1H6L shares certain aspects of its mechanism of action with the parent compound 147B3 but may also inhibit multiple steps in the HSV\u20101 life cycle.<\/jats:p>","DOI":"10.1111\/1348-0421.70005","type":"journal-article","created":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T13:15:03Z","timestamp":1754226903000},"page":"511-521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Antiherpes Simplex Virus Activities of Thiourea\u2010Based Compounds"],"prefix":"10.1111","volume":"69","author":[{"given":"Hiroki","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical, Laboratory of Microbiology and Immunology Gifu Pharmaceutical University Gifu 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