SARS-CoV PLP2 interacts with MDM2 (mouse double minute 2 homolog) to deubiquitinate and stabilize MDM2, approving the degradation of p53 and the suppression of IFN signaling [198]. PEDV infection degrades p53 by upregulation of MDM2 expression [198]. PEDV PLP2 may be responsible for targeting the p53 pathway and inhibiting p53-dependent apoptosis, leading to immune evasion. A recent study determined that TGEV PL1 inhibits the IFN-β expression and interferes with the RIG-1- and STING-mediated signaling pathway through a viral DUB activity [195]. It suggests that different viral proteins are involved in the deubiquitination of host proteins for different CoVs. However, these studies offer a probability to design a common therapeutic against different viral DUBs to reduce the replication and pathogenesis of CoVs. Therefore, further studies are required to understand more about the substrate specificity of these viral DUBs and clarify the precise functions of CoV protease/DUB activity.