Key result
Mouse norovirus-infected macrophage protocol generates early mode-of-action data for novel anti-norovirus small molecules.
Why the study?
Human norovirus causes substantial worldwide disease, and after identifying novel anti-norovirus small molecules, methods are needed to generate early insight into their mode of action.
Describes a protocol for early mechanistic studies of anti-norovirus small molecules using a mouse norovirus in vitro system.
Supports mechanistic evaluation of novel anti-norovirus molecules in vitro; leaves open clinical applicability pending human studies.
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 in vitro 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.
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Dycke et al. (2021) studied Norovirus infection. Norovirus-targeting small molecules was evaluated on Anti-norovirus activity and mode of action in cell culture. A protocol using mouse norovirus-infected macrophages was described to generate early information on the mode of action of novel small molecules with anti-norovirus activity.
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