PDF(Pubmed)
Abstract：
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.
摘要：
传染性软疣（MC）的特征是皮肤病变中含有高度传染性的传染性软疣痘病毒（MCV）。MCV主要感染儿童，使用一种美国食品和药物管理局（FDA）批准的药物设备治疗，但没有批准的药物。MCV无法在体外复制，阻碍了抗病毒药物的评估。这里,我们使用痘苗病毒作为替代品，以提供伯达美尔钠的抗痘病毒特性的证据，一种新的化学实体，和贝达西姆凝胶中的活性物质，10.3%,用于治疗MC的3期开发中的一氧化氮释放局部。我们表明，贝达西姆钠减少痘病毒的复制，通过一种新颖的方法，证明用药物处理的MCV病毒体感染的细胞具有降低的早期基因表达。具体来说,这是通过研究活化B细胞的核因子κ轻链增强子（NF-kB）阻断蛋白MC160作为早期基因的例子来实现的。结果提供了一个合理的独特的抗病毒作用机制，支持增加的MCV分辨率观察到的患者用berdazimer凝胶治疗，10.3％，并描述了一种新颖的方法，该方法克服了对潜在的新MC局部药物的体外研究MCV反应的局限性。
