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10.1038/s41594-021-00653-y

http://scihub22266oqcxt.onion/10.1038/s41594-021-00653-y
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suck abstract from ncbi


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pmid34426697      Nat+Struct+Mol+Biol 2021 ; 28 (9): 747-754
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  • Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome #MMPMID34426697
  • Zhang K; Zheludev IN; Hagey RJ; Haslecker R; Hou YJ; Kretsch R; Pintilie GD; Rangan R; Kladwang W; Li S; Wu MT; Pham EA; Bernardin-Souibgui C; Baric RS; Sheahan TP; D'Souza V; Glenn JS; Chiu W; Das R
  • Nat Struct Mol Biol 2021[Sep]; 28 (9): 747-754 PMID34426697show ga
  • Drug discovery campaigns against COVID-19 are beginning to target the SARS-CoV-2 RNA genome. The highly conserved frameshift stimulation element (FSE), required for balanced expression of viral proteins, is a particularly attractive SARS-CoV-2 RNA target. Here we present a 6.9 A resolution cryo-EM structure of the FSE (88 nucleotides, ~28 kDa), validated through an RNA nanostructure tagging method. The tertiary structure presents a topologically complex fold in which the 5' end is threaded through a ring formed inside a three-stem pseudoknot. Guided by this structure, we develop antisense oligonucleotides that impair FSE function in frameshifting assays and knock down SARS-CoV-2 virus replication in A549-ACE2 cells at 100 nM concentration.
  • |A549 Cells[MESH]
  • |Animals[MESH]
  • |Base Sequence[MESH]
  • |COVID-19/*prevention & control/virology[MESH]
  • |Cell Line, Tumor[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Cryoelectron Microscopy/*methods[MESH]
  • |Frameshift Mutation/*genetics[MESH]
  • |Genome, Viral/genetics[MESH]
  • |Humans[MESH]
  • |Models, Molecular[MESH]
  • |Nucleic Acid Conformation[MESH]
  • |Oligonucleotides, Antisense/*genetics/pharmacology[MESH]
  • |RNA, Viral/chemistry/*genetics/ultrastructure[MESH]
  • |Response Elements/*genetics[MESH]
  • |SARS-CoV-2/*genetics/physiology/ultrastructure[MESH]
  • |Vero Cells[MESH]


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