| Literature DB >> 34426697 |
Kaiming Zhang1,2, Ivan N Zheludev3, Rachel J Hagey4, Raphael Haslecker5, Yixuan J Hou6, Rachael Kretsch7, Grigore D Pintilie1, Ramya Rangan7, Wipapat Kladwang3, Shanshan Li1,2, Marie Teng-Pei Wu5, Edward A Pham4, Claire Bernardin-Souibgui4, Ralph S Baric6,8, Timothy P Sheahan6, Victoria D'Souza5, Jeffrey S Glenn9,10, Wah Chiu11,12,13, Rhiju Das14,15,16.
Abstract
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 Å 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.Entities:
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Year: 2021 PMID： 34426697 PMCID： PMC8848339 DOI： 10.1038/s41594-021-00653-y
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369