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New therapeutic targets are a valuable resource for treating SARS-CoV-2 viral infection. Genome-wide association studies have identified risk loci associated with COVID-19, but many loci are associated with comorbidities and are not specific to host-virus interactions. This study identified and experimentally validated a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 is a component of the RNA exosome. In this study, LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and most of the human RNA exosome components. In addition, the study suggested that targeted depletion of EXOSC2 may be a safe and effective strategy to protect against clinical COVID-19.
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