Abstract：
Cowpox is caused by a DNA virus known as the cowpox virus (CPXV) belonging to the Orthopoxvirus genus in the family Poxviridae. Cowpox is a zoonotic disease with the broadest host range among the known poxviruses. The natural reservoir hosts of CPXV are wild rodents. Recently, the cases of orthopoxviral infections have been increasing worldwide, and cowpox is considered the most common orthopoxviral infection in Europe. Cowpox is often a self-limiting disease, although cidofovir or anti-vaccinia gammaglobulin can be used in severe and disseminated cases of human cowpox. In this computational study, a molecular docking analysis of thymine- and arabinofuranosyl-thymine-related structures (1-21) on two cowpox-encoded proteins was performed with respect to the cidofovir standard and a 3D ligand-based pharmacophore model was generated. Three chemical structures (PubChem IDs: 123370001, 154137224, and 90413364) were identified as potential candidates for anti-cowpox agents. Further studies combining in vitro and in silico molecular dynamics simulations to test the stability of these promising compounds could effectively improve the future design of cowpox virus inhibitors, as molecular docking studies are not sufficient to consider a ligand a potential drug.
摘要：
牛痘是由一种称为牛痘病毒（CPXV）的DNA病毒引起的，该病毒属于痘病毒科中的正痘病毒属。牛痘是已知痘病毒中具有最广泛宿主范围的人畜共患疾病。CPXV的天然水库宿主是野生啮齿动物。最近,正痘病毒感染的病例在世界范围内一直在增加，牛痘被认为是欧洲最常见的正痘病毒感染。牛痘通常是一种自限性疾病,虽然西多福韦或抗痘苗球蛋白可用于严重和传播的人牛痘病例。在这项计算研究中，针对西多福韦标准品,对两种牛痘编码蛋白上的胸腺嘧啶-和阿拉伯呋喃糖基-胸腺嘧啶相关结构(1-21)进行了分子对接分析,并生成了基于3D配体的药效团模型.三种化学结构(PubChemID:123370001、154137224和90413364)被鉴定为抗牛痘剂的潜在候选物。结合体外和计算机分子动力学模拟来测试这些有前途的化合物的稳定性的进一步研究可以有效地改善牛痘病毒抑制剂的未来设计，因为分子对接研究不足以将配体视为潜在药物。
