Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Novan, Durham, NC 27703, USA.
Viruses. 2023 Nov 30;15(12):2360. doi: 10.3390/v15122360.
Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication.
传染性软疣（MC）的特征是皮肤损伤含有高度传染性的传染性软疣病毒（MCV）。MCV 主要感染儿童，目前有一款获得美国食品和药物管理局（FDA）批准的药物-器械治疗方法，但没有批准的药物。由于 MCV 无法在体外复制，评估抗病毒药物的效果受到阻碍。在这里，我们使用牛痘病毒作为替代物，为新化学实体贝达西莫钠和贝达西莫凝胶的活性物质 10.3%（一种用于治疗 MC 的处于 3 期开发阶段的释放一氧化氮的局部治疗药物）的抗痘病毒特性提供证据。我们表明贝达西莫钠可减少痘病毒复制，并通过一种新方法证明感染药物处理的 MCV 病毒的细胞的早期基因表达减少。具体来说，通过研究核因子 kappa 轻链增强子的 B 细胞激活（NF-kB）阻断蛋白 MC160 作为早期基因的一个例子来实现这一目标。这些结果提供了一种合理的独特的抗病毒作用机制，支持接受贝达西莫凝胶 10.3%治疗的患者中观察到的 MCV 分辨率增加，并描述了一种克服在体外研究潜在新 MC 局部治疗药物对 MCV 反应的局限性的新方法。
