Abstract
The increasing global prevalence of mosquito-borne viruses has emerged as a significant threat to human health and life. Identifying receptors for these viruses is crucial for improving our knowledge of viral pathogenesis and developing effective antiviral strategies. The widespread application of CRISPR-Cas9 screening have led to the discovery of many mosquito-borne virus receptors. The revealed structures of virus-receptor complexes also provide important information for understanding their interaction mechanisms. This review provides a comprehensive summary of both conventional and novel approaches for identifying new viral receptors and the putative entry factors of the most prevalent mosquito-borne viruses within the Flaviviridae, Togaviridae, and Bunyavirales. At the same time, we emphasize the common receptors utilized by these viruses for entry into both vertebrate hosts and mosquito vectors. We discuss promising avenues for developing anti-mosquito-borne viral strategies that target these receptors. Notably, targeting universal receptors of specific mosquito-borne viruses in both vertebrates and mosquitoes offers dual benefits for disease prevention. Additionally, the widespread use of AI-based machine learning and protein structure prediction will accelerate the identification of new viral receptors and provide new avenues for antiviral drug discovery.