KU Leuven - Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
Antivir Chem Chemother. 2021 Jan-Dec;29:20402066211025175. doi: 10.1177/20402066211025175.
Human norovirus is the main cause of viral gastroenteritis, resulting annually in ∼ 700 million infections and 200,000 deaths, of whom most are children <5 years. Mouse norovirus-infected macrophages are the most widely used system to screen and characterize the antiviral effect of norovirus-targeting small molecules. We have previously established antiviral assays using this system, identified novel inhibitors and performed additional studies in order to have a first insight into their mechanism of action. After the identification of novel small molecules with anti-norovirus activity (part 1 of this protocol), we here describe the logical next step which entails the generation of early information of their mode of action. This information together with a continuous improvement of the potency of compounds will contribute to the optimization of a compound class towards in vivo efficacy and a successful preclinical development.
人类诺如病毒是病毒性肠胃炎的主要病因，每年导致约 7 亿感染和 20 万人死亡，其中大多数是 5 岁以下的儿童。感染鼠诺如病毒的巨噬细胞是筛选和表征诺如病毒靶向小分子抗病毒作用的最广泛应用系统。我们之前使用该系统建立了抗病毒检测方法，鉴定了新型抑制剂，并进行了进一步的研究，以便初步了解其作用机制。在鉴定出具有抗诺如病毒活性的新型小分子（本方案第 1 部分）后，我们在这里描述了接下来的合理步骤，即生成其作用模式的早期信息。这些信息以及化合物效力的不断提高将有助于优化化合物类别以实现体内疗效，并成功进行临床前开发。
