Computer-aided approaches for human norovirus drug discovery: a comprehensive review

The absence of 3D structures for most viral proteins has limited the identification of novel chemotypes through CADD approaches. Furthermore, the lack of biological validation after <i>in silico</i> studies may slow down progress in this field, as researchers might focus on compounds that seem promising only at the computational level. Emerging systems such as human intestinal enteroids, together with AI/ML augmented CADD, can accelerate optimization and triage of non-nucleoside and covalent protease inhibitors.