The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex

There is an urgent need for a molecular understanding of how SARS-CoV-2 influences the machineries of the host cell. Herein, we focused our attention on the capacity of the SARS-CoV-2 protein NSP2 to bind the human 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of gene expression. Using in vitro interaction assays, our data demonstrate that NSP2 physically associates with both 4EHP and a central segment in GIGYF2 in the cytoplasm. We also provide functional evidence showing that NSP2 impairs the function of GIGYF2 in mediating translation repression using reporter-based assays. Collectively, these data reveal the potential impact of NSP2 on the post-transcriptional silencing of gene expression in 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.