MAPPING OF ANTIVIRAL TARGETS IN THE ALPHAVIRUS PROTEOME AND ESTABLISHMENT OF RELEVANT INFECTION MODELS TO ASSESS ANTIVIRAL EFFECTS

Alphaviruses cause severe diseases such as encephalitis and arthritis. Some alphaviruses, including
the chikungunya virus (CHIKV), are significant global health threats because of their high disease
burden, their (re-)emergence, and the lack of vaccines or therapeutics. In this research proposal
we aim to identify new druggable targets in the replication cycle of alphaviruses by a
chemobiology approach. The study of these antiviral targets will reveal fundamental insights in the
replication of alphaviruses. Furthermore, these targets could provide a promising starting point to
develop antiviral therapy for alphavirus infections. In the second part of this research proposal,
CHIKV inhibitors that block these targets will be validated in relevant infection models. We will
study the effect of antiviral molecules with different modes of action in a CHIKV-induced arthritis
mouse model. As neurological complications are the main cause for severe morbidity and
mortality in acute CHIKV infections, we will also establish in vitro neurological infection models
using stem-cell derived neuronal cell cultures.