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10.1038/s41467-020-19843-1

http://scihub22266oqcxt.onion/10.1038/s41467-020-19843-1
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33247108!7699647!33247108
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suck abstract from ncbi


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pmid33247108      Nat+Commun 2020 ; 11 (1): 6041
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  • Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates #MMPMID33247108
  • Savastano A; Ibanez de Opakua A; Rankovic M; Zweckstetter M
  • Nat Commun 2020[Nov]; 11 (1): 6041 PMID33247108show ga
  • The etiologic agent of the Covid-19 pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral membrane of SARS-CoV-2 surrounds a helical nucleocapsid in which the viral genome is encapsulated by the nucleocapsid protein. The nucleocapsid protein of SARS-CoV-2 is produced at high levels within infected cells, enhances the efficiency of viral RNA transcription, and is essential for viral replication. Here, we show that RNA induces cooperative liquid-liquid phase separation of the SARS-CoV-2 nucleocapsid protein. In agreement with its ability to phase separate in vitro, we show that the protein associates in cells with stress granules, cytoplasmic RNA/protein granules that form through liquid-liquid phase separation and are modulated by viruses to maximize replication efficiency. Liquid-liquid phase separation generates high-density protein/RNA condensates that recruit the RNA-dependent RNA polymerase complex of SARS-CoV-2 providing a mechanism for efficient transcription of viral RNA. Inhibition of RNA-induced phase separation of the nucleocapsid protein by small molecules or biologics thus can interfere with a key step in the SARS-CoV-2 replication cycle.
  • |Animals[MESH]
  • |Antiviral Agents/pharmacology/therapeutic use[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/epidemiology/*virology[MESH]
  • |Coronavirus Nucleocapsid Proteins/antagonists & inhibitors/*metabolism[MESH]
  • |Coronavirus RNA-Dependent RNA Polymerase/metabolism[MESH]
  • |HeLa Cells[MESH]
  • |Humans[MESH]
  • |Insecta[MESH]
  • |Intravital Microscopy[MESH]
  • |Microscopy, Fluorescence[MESH]
  • |Molecular Dynamics Simulation[MESH]
  • |Pandemics/prevention & control[MESH]
  • |Phosphoproteins/antagonists & inhibitors/metabolism[MESH]
  • |RNA, Viral/antagonists & inhibitors/*metabolism[MESH]
  • |SARS-CoV-2/drug effects/*physiology[MESH]
  • |Viral Transcription/drug effects/physiology[MESH]


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