In this study, we demonstrate that SARS-CoV-2 N has the capacity to inhibit two important innate antiviral pathways, PKR and OAS/RNase L. It is logical that SARS-CoV-2 N plays an important role in the high transmissibility and pathogenicity of SARS-CoV-2, which are two viral determinants of the COVID-19 pandemic. This evidence concerns the gene RNASEL and COVID-19.