Infections with Herpes simplex viruses (HSV) belong to the most common human diseases worldwide, resulting in symptoms ranging from painful, but commonly self-limiting lesions of the orofacial or genital tract to severe infections of the eye or life-threatening generalized infections. Frequent HSV-reactivations at the eye may lead to the development of herpetic stromal keratitis, which is one of the major causes of infectious blindness in developed countries. The vast majority of life-threatening generalized infections occur in immunocompromised individuals, such as transplant recipients or patients suffering from advanced human immunodeficiency virus (HIV) infection with concurrent HSV-reactivation. Over the past decades, Acyclovir (ACV) became the golden standard for the treatment of HSV infections. However, long-term antiviral treatment, as it is required mainly in immunocompromised patients, led to the emergence of resistances towards ACV and other antivirals. Therefore, there is a clear need for the development of new potent antivirals which combine good oral bioavailability and tolerability with low side effects. In the current study we present SC93305 as a novel potent antiviral substance that proved to be highly effective not only against different HSV-1 and HSV-2 strains but also towards ACV- and multi-resistant HSV-1 and HSV-2 isolates. SC93305 shows comparable antiviral activity as reported for ACV and very importantly it does not interfere with the activation of specific immune cells. Here we report that SC93305 does not affect the biological function of dendritic cells (DC), the most potent antigen presenting cells of the immune system to induce antiviral immune responses, nor T cell stimulation or the release of inflammatory cytokines. Thus, SC93305 is a new and promising candidate for the treatment of HSV-1 and HSV-2 infections and in particular also for the inhibition of drug-resistant HSV-1/2 strains.

单纯疱疹病毒（HSV）感染是世界范围内最常见的人类疾病，其症状范围从口腔或生殖道的疼痛但通常是自限性病变到严重的眼部感染或危及生命的全身性感染。眼内频繁的HSV重新激活可能导致疱疹性基质性角膜炎的发展，这是发达国家感染性失明的主要原因之一。绝大多数威胁生命的全身感染发生在免疫功能低下的个体中，例如移植受者或患有晚期人类免疫缺陷病毒（HIV）感染并同时发生HSV激活的患者。在过去的几十年中，阿昔洛韦（ACV）成为治疗HSV感染的黄金标准。但是，长期抗病毒治疗，因为主要在免疫功能低下的患者中需要，导致出现了对ACV和其他抗病毒药的耐药性。因此，显然需要开发新的有效的抗病毒药，其将良好的口服生物利用度和耐受性与低副作用相结合。在当前的研究中，我们提出SC93305作为一种新型的有效抗病毒物质，不仅对不同的HSV-1和HSV-2菌株具有很高的功效，而且对ACV和多重耐药的HSV-1和HSV-2分离株也具有很高的功效。SC93305显示出与ACV相当的抗病毒活性，非常重要的是它不干扰特定免疫细胞的激活。在这里，我们报道SC93305不会影响树突状细胞（DC）的生物学功能，免疫系统中最有效的抗原呈递细胞，可以诱导抗病毒免疫反应，也不能刺激T细胞或释放炎性细胞因子。因此，SC93305是治疗HSV-1和HSV-2感染，特别是抑制耐药性HSV-1 / 2菌株的新的有希望的候选者。