While our model lacks the context of other viral proteins that would be present in a bona fide infection, this mechanism could nonetheless unveil the impact of NSP2 on the post-transcriptional silencing of gene expression of human cells, pointing out 4EHP-GIGYF2 targeting as a possible strategy of SARS-CoV-2 to take over the silencing machinery and to suppress host defenses. This evidence concerns the gene EIF4E2 and infection.