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首页> 外文期刊>Antimicrobial agents and chemotherapy. >A novel target and approach for identifying antivirals against molluscum contagiosum virus
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A novel target and approach for identifying antivirals against molluscum contagiosum virus

机译：鉴定针对传染性软体动物的抗病毒药的新目标和方法

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摘要

The dermatological disease molluscum contagiosum (MC) presents as lesions restricted solely to the skin. The poxvirus molluscum contagiosum virus (MCV) is responsible for this skin disease that is easily transmitted through casual contact among all populations, with greater frequency in children and immunosuppressed individuals. In addition, sexual transmission of MCV in adolescents and adults is a health concern. Although the skin lesions ultimately resolve in immunocompetent individuals, they can persist for extended periods, be painful, and result in scarring. Treatment is problematic, and there is no drug that specifically targets MCV. The inability of MCV to propagate in cell culture has impeded drug development. To overcome these barriers, we integrated three new developments. First, we identified a new MCV drug target (mD4) that is essential for processive DNA synthesis in vitro. Second, we discovered a small chemical compound that binds to mD4 and prevents DNA synthesis in vitro. Third, and most significant, we engineered a hybrid vaccinia virus (mD4-VV) in which the natural vaccinia D4 (vD4) gene is replaced by the mD4 target gene. This hybrid virus is dependent on mD4 for viral growth in culture and is inhibited by the small compound. This target system provides, for the first time, a platform and approach for the discovery and evaluation of new therapeutics that can be used to treat MC.
机译：皮肤病性传染性软体动物（MC）表现为仅局限于皮肤的病变。痘病毒感染性皮疹病毒（MCV）引起了这种皮肤病，该病很容易通过所有人群之间的偶然接触传播，在儿童和免疫抑制的个体中发病率更高。另外，在青少年和成年人中MCV的性传播是健康问题。尽管皮肤病变最终会在具有免疫能力的个体中消退，但它们可以持续较长时间，很痛苦并导致瘢痕形成。治疗存在问题，并且没有专门针对MCV的药物。 MCV不能在细胞培养物中繁殖已经阻碍了药物开发。为了克服这些障碍，我们整合了三个新的发展。首先，我们确定了新的MCV药物靶标（mD4），该靶标对于体外进行性DNA合成至关重要。其次，我们发现了一种与mD4结合并阻止体外DNA合成的小型化合物。第三，也是最重要的是，我们设计了一种混合牛痘病毒（mD4-VV），其中天然牛痘D4（vD4）基因被mD4目标基因替代。这种杂合病毒依赖于mD4的病毒在培养基中生长，并被这种小化合物抑制。该目标系统首次为发现和评估可用于治疗MC的新疗法提供了平台和方法。

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