Feline infectious peritonitis (FIP) is the most feared infectious cause of death in cats, caused by the feline infectious peritonitis virus (FIPV). FIPV is a virulent mutant of the feline enteric coronavirus, an ubiquitous but harmless intestinal virus. The mutation provides FIPV with tools to replicate in monocytes, in which it can be spread over the whole body, resulting in a fatal, systemic disorder. As for other coronaviruses, curative measures are not available. This is not only due to the many unresolved questions in the virus-cell interactions and pathogenesis, but also due to fact that these RNA viruses have a remarkable adaptive character, which can explain the failure of singledrug approaches so far. Previous research performed by our group created novel insights and tools that finally opens the opportunity for more in-depth research on the coronavirus-cell interactions and identification of multiple antivirals. In line with this research, the present project will focus on the early virus-cell interactions, by 1) identifying the receptor using co-immunoprecipitation with receptor-binding S1-Fc fusion proteins, and by 2) characterizing a post-entry step involving a new serine protease activity that is even conserved among all tested nidoviruses so far. These studies will not only solve some missing links in the coronavirus replication strategies and FIP pathogenesis, but will also allow a multi-target approach in antiviral development against coronaviruses.