Host factors and drug targets in alphavirus and nidovirus replication

EUVIRNA ESR-10

Project description
This project is aimed at developing novel antiviral strategies and drug leads, which are currently lacking for alphaviruses (Chikungunya virus) and nidoviruses (SARS- and other human coronaviruses). Mechanism of action studies will be performed for compounds that inhibit Chikungunya virus replication (identified in the laboratory of prof. Johan Neyts in Leuven, Belgium) by genotyping drug-resistant mutants and in-depth follow-up studies. Furthermore, the possibility of blocking alpha- and nidovirus replication by targeting host factors (instead of viral targets) will be explored. This approach could circumvent the common problem of antiviral drug resistance in RNA viruses, which is due to their intrinsic high mutation rate. Recently performed and ongoing (medium-scale) siRNA screens, e.g. targeting cellular signaling and transport pathways or cellular proteins that interact with the viral replication machinery, have already identified several factors that affect alpha- and nidovirus replication. A number of these virus-host interactions will be studied in detail, in particular to understand their role in virus replication and their suitability as a potential target for antiviral strategies. In parallel, more hits will be obtained by more extensive (genome-wide) siRNA screens, which will be performed in collaboration with the group of prof. Ralf Bartenschlager (Heidelberg, Germany). Finally, it will be investigated whether certain (specific) host factors that have been shown to affect the replication of other viruses play a role in the nido- and alphavirus life cycle as well.

Host institute
Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology
Supervisor: Prof. dr. Eric Snijder

Position filled.