Evasion of host immune responses is necessary for the successful propagation of a virus. Mechanisms employed by CoVs to evade the immune response could provide insights into how the immune system, and NK cells in particular, responds to SARS-CoV-2. CoVs have been shown to target components of the innate IFN response, employing non-structural proteins (nsps), structural proteins, and accessory proteins to achieve this goal. Nsp16 methylates viral RNA therefore preventing recognition by MDA5 and dampening type I IFN production (116). Nsps also suppress type I IFN responses via the inhibition of the transcription factor STAT1 mRNA transcription (nsp1) and deubiquitination of transcription factors like Interferon Regulatory Transcription Factor (IRF)3 (nsp3) (116). Moreover, viral-encoded accessory proteins from SARS-CoV-1 open reading frame (ORF)3b and MERS-CoV ORF4a/4b also block IFN production and signaling (116). In addition, the MERS-CoV ORF6-encoded protein blocks p-STAT1 import, thus blocking IFN signaling (116). Finally, the structural M protein of MERS-CoV (27) physically sequesters kinase proteins RIG-I, TBK1, IKKe, and TRAF3 and the SARS-CoV-1 N protein inhibits Activator Protein (AP)-1 signaling, protein kinase R function, and NFκB activation, all of which act to impede IFN responses (117). In vivo murine studies report young mice rapidly clear SARS-CoV-1 infection, while old mice do not and that this discrepancy is due to a delay in type I IFN. Furthermore, early administration of IFN-β induces a stronger immune response and reduces mortality in old mice (118). Since type I IFNs are critical for NK cell activation and effector functions, it is possible that NK cell-mediated clearance of SARS-CoV-2 is being subverted by these mechanisms. Further research into the role of NK cells in CoV clearance and potential immune evasion mechanisms are necessary to inform therapeutic development and use.