Abstract:Viruses attach and invade target-cells by binding to a specific receptor(s) on the surface of target-cells, and hijack the cellular replication machinery to complete the life cycle. The cellular receptor is the gateway for viruses to infect host cells, and the structure and function of cellular receptors and the mechanism of virus entry mediated by cellular receptors have been one of the hotspots of molecular virology. The discovery of cellular receptors is helpful to understand the pathogenesis of viruses and develop prevention and control strategies for viral diseases. In recent years, the progress in screening functional viral receptors using functional genomics has greatly expanded our understanding of the mechanism of virus entry. At present, widely used functional viral receptor screening strategies include RNA interference, random retroviral insertional mutagenesis using haploid cell lines and the recently emerging CRISPR/Cas9 system. In this review, three novel strategies of functional viral receptors screening are systematically introduced and compared, and their applications, advantages and disadvantages are summarized to provide references for relevant researchers.