BACKGROUND HSV-1 is a common pathogen that infects 50-90% of the human population worldwide. HSV-1 causes numerous infection-related diseases, some of which are severely life-threatening. There are antiviral medications with activity against HSV-1. However, with the emergence of drug-resistant mutant strains of HSV-1, there is an urgent need to develop new effective anti-HSV-1 agents. METHODS Therefore, we screened a chemical library of approximately 1500 compounds to identify inhibitors of HSV-1-induced toxicity for further drug development. Moreover, we performed several experiments, including western blot analysis, Q-PCR analysis and luciferase activity assay, to explore the antiviral mechanism of the candidates. RESULTS Here, we identified a small molecule, mitoxantrone dihydrochloride, with potency against HSV-1-induced toxicity. Furthermore, the viral titers and expression levels of HSV-1 viral proteins were potently reduced by the presence of MD in many cell lines. Using Q-PCR analysis, we found that MD efficiently reduced the transcription of viral genes that are essential for DNA synthesis, namely, UL5, UL9, UL29, UL30, UL42 and UL52. Notably, MD also significantly inhibited the transcription of the immediate early genes ICP0, ICP22, ICP27 and ICP47, all of which are required for the expression of early and late viral gene products. Using immunofluorescence and western blot analysis, we found that the antiviral effect of MD was independent of the activation of the NF-κB and MAPK pathways. Furthermore, we found that the reduction in the transcription of viral immediate early genes was not related to the promoter activities of ICP0. CONCLUSIONS Therefore, the identification of compound MD as an inhibitor of toxicity induced by HSV-1 highlights its potential use in the development of novel anti-HSV-1 drugs.

中文翻译：

---

盐酸米托蒽醌对人单纯疱疹病毒的抗病毒活性是通过抑制病毒立即早期基因介导的。

背景技术HSV-1是一种常见的病原体，可感染全世界50-90％的人口。HSV-1会导致许多与感染相关的疾病，其中一些严重威胁生命。有抗HSV-1活性的抗病毒药物。然而，随着HSV-1耐药突变株的出现，迫切需要开发新的有效的抗HSV-1药物。方法因此，我们筛选了大约1500种化合物的化学文库，以鉴定HSV-1诱导的毒性抑制剂，以进一步开发药物。此外，我们进行了一些实验，包括蛋白质印迹分析，Q-PCR分析和萤光素酶活性测定，以探索候选人的抗病毒机制。结果在这里，我们确定了一种小分子米托蒽醌二盐酸盐，具有对抗HSV-1诱导的毒性的作用。此外，许多细胞系中MD的存在有效降低了HSV-1病毒蛋白的病毒滴度和表达水平。使用Q-PCR分析，我们发现MD有效降低了DNA合成所必需的病毒基因的转录，即UL5，UL9，UL29，UL30，UL42和UL52。值得注意的是，MD还显着抑制了早期早期基因ICP0，ICP22，ICP27和ICP47的转录，这些都是早期和晚期病毒基因产物表达所必需的。使用免疫荧光和蛋白质印迹分析，我们发现MD的抗病毒作用与NF-κB和MAPK途径的激活无关。此外，我们发现病毒立即早期基因转录的减少与ICP0的启动子活性无关。结论因此，