Herpes simplex virus type 1 (HSV-1) infections are prevalent illnesses that can cause mucocutaneous ulcerative disease, keratitis, and genital herpes. In patients with compromised immune systems, the infection can lead to serious problems, such as encephalitis. Additionally, neonatal infections can cause brain problems and even death. Current first-line antiviral drugs are nucleoside analog inhibitors that target viral polymerase, and resistant strains have emerged. As a result, new drugs with distinct action modes are needed. Recent research indicates that cyclin-dependent kinases (CDKs) are prospective antiviral targets. Thus, CDK inhibitors may be effective antiviral agents against HSV-1 infection. In this study, we examined a panel of CDK inhibitors that target CDKs in the present study. BMS-265246 (BMS), a CDK 1/2 inhibitor, was found to effectively limit HSV-1 multiplication in Vero, HepG2, and Hela cells. A mechanism of action study suggested that BMS inhibits the early stages of viral replication when added early in the viral infection. The suppression of multiple steps in viral replication by BMS was revealed when HSV-1 infected cells were treated at different time periods in the viral life cycle. Our results suggest that BMS is a potent anti-HSV-1 agent and unique in that it may interfere with multiple steps in HSV-1 replication.

中文翻译：

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BMS-265246 是一种细胞周期蛋白依赖性激酶抑制剂，可抑制 1 型单纯疱疹病毒的感染

1 型单纯疱疹病毒 (HSV-1) 感染是一种常见疾病，可导致皮肤粘膜溃疡病、角膜炎和生殖器疱疹。对于免疫系统受损的患者，感染可能会导致严重的问题，例如脑炎。此外，新生儿感染可能导致大脑问题甚至死亡。目前的一线抗病毒药物是针对病毒聚合酶的核苷类似物抑制剂，并且已经出现了耐药菌株。因此，需要具有不同作用模式的新药。最近的研究表明细胞周期蛋白依赖性激酶（CDK）是潜在的抗病毒靶点。因此，CDK抑制剂可能是对抗HSV-1感染的有效抗病毒剂。在这项研究中，我们检查了一组针对本研究中的 CDK 的 CDK 抑制剂。BMS-265246 (BMS) 是一种 CDK 1/2 抑制剂，被发现可有效限制 Vero、HepG2 和 Hela 细胞中的 HSV-1 增殖。作用机制研究表明，在病毒感染早期添加 BMS 可以抑制病毒复制的早期阶段。当HSV-1感染的细胞在病毒生命周期的不同时间段进行处理时，BMS对病毒复制的多个步骤的抑制被揭示。我们的结果表明，BMS 是一种有效的抗 HSV-1 药物，其独特之处在于它可能干扰 HSV-1 复制的多个步骤。