RT Journal Article
SR Electronic
T1 Antisense oligonucleotides target a nearly invariant structural element from the SARS-CoV-2 genome and drive RNA degradation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.18.304139
DO 10.1101/2020.09.18.304139
A1 Valeria Lulla
A1 Michal P. Wandel
A1 Katarzyna J. Bandyra
A1 Tom Dendooven
A1 Xiaofei Yang
A1 Nicole Doyle
A1 Stephanie Oerum
A1 Sara O’Rourke
A1 Felix Randow
A1 Helena J. Maier
A1 William Scott
A1 Yiliang Ding
A1 Andrew E. Firth
A1 Kotryna Bloznelyte
A1 Ben F. Luisi
YR 2020
UL http://biorxiv.org/content/early/2020/09/19/2020.09.18.304139.abstract
AB The SARS-CoV-2 virus contains an unusually large, single-stranded RNA genome that is punctuated with structured elements of unknown function, such as the s2m element located in the 3’ untranslated region. The evolutionary conservation of the s2m element and its occurrence in all viral subgenomic transcripts implicates a key role in the viral infection cycle. In order to exploit this element as a potential therapeutic target, we have designed antisense “gapmer” oligonucleotides that efficiently base-pair to the s2m region. These oligonucleotides, composed of locked nucleic acids (LNA) flanking a central DNA core, successfully remodel the s2m structure and induce sequence-specific RNA cleavage by RNase H in vitro. Gapmers are also effective in human cells as they reduce the fluorescence signal in GFP reporter assays and cause a dose-dependent reduction in replication in a model replicon system based on a human astrovirus. Overall, these oligonucleotides show promise as anti-viral agents and may serve as a helpful starting point to develop treatments for COVID-19.Competing Interest StatementThe authors have declared no competing interest.