Proteomic analysis identifies the RNA helicase DDX3X as a host target against SARS-CoV-2 infection

Antiviral Res. 2021 Mar 26;190:105064. doi: 10.1016/j.antiviral.2021.105064. Online ahead of print.ABSTRACTCOVID-19 is currently a highly pressing health threat and therapeutic strategies to mitigate the infection impact are urgently needed. Characterization of the SARS-CoV-2 interactome in infected cells may represent a powerful tool to identify cellular proteins hijacked by viruses for their life cycle and develop host-oriented antiviral therapeutics. Here we report the proteomic characterization of host proteins interacting with SARS-CoV-2 Nucleoprotein in infected Vero E6 cells. We identified 24 high-confidence proteins mainly playing a role in RNA metabolism and translation, including RNA helicases and scaffold proteins involved in the formation of stress granules, cytoplasmic aggregates of messenger ribonucleoproteins that accumulate as a result of stress-induced translation arrest. Analysis of stress granules upon SARS-CoV-2 infection showed that these structures are not induced in infected cells, neither eIF2α phosphorylation, an upstream event leading to stress-induced translation inhibition. Notably, we found that G3BP1, a stress granule component that associates with the Nucleoprotein, is required for efficient SARS-CoV-2 replication. Moreover, we showed that the Nucleoprotein-interacting RNA helicase DDX3X colocalizes with viral RNA foci and its inhibition by small molecules or small interfering RNAs significantly reduces viral replication. Altogether, these resu...

Source: Antiviral Research - March 30, 2021 Category: Virology Authors: Fabiola Ciccosanti Martina Di Rienzo Alessandra Romagnoli Francesca Colavita Giulia Refolo Concetta Castilletti Chiara Agrati Annalaura Brai Fabrizio Manetti Lorenzo Botta Maria Rosaria Capobianchi Giuseppe Ippolito Mauro Piacentini Gian Maria Fimia Source Type: research