Nervous necrosis virus (NNV) is a prominent pathogen that infects a variety of cultured marine fish, leading to nerve necrosis and a high mortality rate. At present, there are many studies on the genetics and structure of nervous necrosis virus, but its pathogenic mechanism remains unclear. To investigate this mechanism, in this study native NNV coat protein (NNVCP) was used to screen for proteins that bind to NNVCP in grouper tissues by immunoprecipitation (IP) assay. The initial results identified various proteins that can interact with NNVCP and may function as putative receptor or co-receptor, cytoskeleton, glucose metabolism and ATP generation, immunity, mitochondrial ion regulation and ribosomal proteins. The putative receptor or co-receptor can help virus to invade the host cell and then complete the replication process. Cytoskeleton contributes to the spread of the virus within the cell. The identified proteins participating in sugar metabolic pathways and calcium signalling may affect the ATP energy balance and may also cause host cell apoptosis and necrosis. Further experiments are needed to verify the role and authenticity of the proteins found to interact with nervous necrosis virus in this study.