To investigate the common characteristics of mammalian virus co-receptors, this study collected 277 pairs of viral co-receptor combinations based on the data from ViralReceptor database. We investigated the structural, functional, evolutionary and tissue expression characteristics of mammalian virus co-receptors and compared them with combinations of viral receptors derived from different mammalian viruses, as well as randomly selected human proteins. The results showed that in comparison to other protein pairs, mammalian virus co-receptors exhibited higher functional similarity, higher ratio of interaction in the host protein interaction network, and higher co-expression levels in common human tissues. This study demonstrates that mammalian virus co-receptors share common features such as functionality, expression, and interaction, with the expectation that these findings will provide a reference for the discovery and identification of virus receptors.