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10.1016/j.antiviral.2021.105064

http://scihub22266oqcxt.onion/10.1016/j.antiviral.2021.105064
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suck abstract from ncbi


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pmid33781803      Antiviral+Res 2021 ; 190 (ä): 105064
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  • Proteomic analysis identifies the RNA helicase DDX3X as a host target against SARS-CoV-2 infection #MMPMID33781803
  • Ciccosanti F; Di Rienzo M; Romagnoli A; Colavita F; Refolo G; Castilletti C; Agrati C; Brai A; Manetti F; Botta L; Capobianchi MR; Ippolito G; Piacentini M; Fimia GM
  • Antiviral Res 2021[Jun]; 190 (ä): 105064 PMID33781803show ga
  • COVID-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 eIF2alpha 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 results indicate that SARS-CoV-2 subverts the stress granule machinery and exploits G3BP1 and DDX3X for its replication cycle, offering groundwork for future development of host-directed therapies.
  • |*COVID-19 Drug Treatment[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |COVID-19/*metabolism/virology[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |DEAD-box RNA Helicases/*metabolism[MESH]
  • |DNA Helicases[MESH]
  • |Eukaryotic Initiation Factor-2/metabolism[MESH]
  • |Host-Pathogen Interactions[MESH]
  • |Humans[MESH]
  • |Poly-ADP-Ribose Binding Proteins/genetics/metabolism[MESH]
  • |Proteomics/methods[MESH]
  • |RNA Helicases[MESH]
  • |RNA Recognition Motif Proteins/metabolism[MESH]
  • |RNA, Small Interfering/metabolism[MESH]
  • |RNA, Viral/metabolism[MESH]
  • |SARS-CoV-2/metabolism[MESH]
  • |Vero Cells[MESH]


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