This thesis explores the use of clinical CMV isolates in the validation of antiviral effects against CMV infection of human CNS models in the context of cCMV disease. Next, it elucidates the use of advanced human neuronal models in CMV research. Lastly, it proposes the application of these neuronal models in the testing of novel antiviral drugs.This thesis systematically describes the culture of neural organoids (NOs) in their use for neurodevelopmental research. Different human NO models are discussed together with their characteristics and applications. This thesis focusses then on human NOs as models for virus research and provides insights into the currently most applied NO models in virus research studies as well as their outcomes. Next, it explores techniques to increase virus yields cell lines, optimise virus concentrations and cryopreserve virus titres of clinical CMV isolates. Furter, this thesis elucidates on differences in antiviral efficacy of blocking CMV infection in a regionalised NO model. Letermovir, ganciclovir and maribavir are assessed in different concentrations in 2D and 3D neural models, using a clinical CMV isolate and a mCherry-tagged BAC strain. Next, the inhibition efficacy of halofuginone hydrobromide on different viruses, including CMV, in different human organotypic models is discussed. Finally, the advantages and challenges of using clinical isolates in CMV research are discussed, together with NOs as models of the developing human brain. The current antiviral therapies and alternative strategies to treat and/or prevent CMV infection in vulnerable populations are also discussed
