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10.1038/s41594-021-00619-0

http://scihub22266oqcxt.onion/10.1038/s41594-021-00619-0
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34158638!8772433!34158638
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suck abstract from ncbi


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pmid34158638      Nat+Struct+Mol+Biol 2021 ; 28 (7): 573-582
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  • Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs #MMPMID34158638
  • Kern DM; Sorum B; Mali SS; Hoel CM; Sridharan S; Remis JP; Toso DB; Kotecha A; Bautista DM; Brohawn SG
  • Nat Struct Mol Biol 2021[Jul]; 28 (7): 573-582 PMID34158638show ga
  • SARS-CoV-2 ORF3a is a putative viral ion channel implicated in autophagy inhibition, inflammasome activation and apoptosis. 3a protein and anti-3a antibodies are found in infected patient tissues and plasma. Deletion of 3a in SARS-CoV-1 reduces viral titer and morbidity in mice, suggesting it could be an effective target for vaccines or therapeutics. Here, we present structures of SARS-CoV-2 3a determined by cryo-EM to 2.1-A resolution. 3a adopts a new fold with a polar cavity that opens to the cytosol and membrane through separate water- and lipid-filled openings. Hydrophilic grooves along outer helices could form ion-conduction paths. Using electrophysiology and fluorescent ion imaging of 3a-reconstituted liposomes, we observe Ca(2+)-permeable, nonselective cation channel activity, identify mutations that alter ion permeability and discover polycationic inhibitors of 3a activity. 3a-like proteins are found across coronavirus lineages that infect bats and humans, suggesting that 3a-targeted approaches could treat COVID-19 and other coronavirus diseases.
  • |*Cryoelectron Microscopy[MESH]
  • |*Nanostructures/chemistry/ultrastructure[MESH]
  • |*SARS-CoV-2/chemistry/ultrastructure[MESH]
  • |Animals[MESH]
  • |Calcium/metabolism[MESH]
  • |Chiroptera/virology[MESH]
  • |Coronaviridae[MESH]
  • |Electrophysiology[MESH]
  • |Fluorescence[MESH]
  • |Humans[MESH]
  • |Ion Transport[MESH]
  • |Liposomes[MESH]
  • |Models, Molecular[MESH]
  • |Open Reading Frames[MESH]
  • |Optical Imaging[MESH]
  • |Reproducibility of Results[MESH]
  • |Sequence Homology[MESH]
  • |Viral Proteins/chemistry/ultrastructure[MESH]


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