Restriction of SARS-CoV-2 Replication by Targeting Programmed -1 Ribosomal Frameshifting In Vitro

  • bioRxiv. 2020 Oct 21;2020.10.21.349225. doi: 10.1101/2020.10.21.349225.
Yu Sun  1 ,  Laura Abriola  2 ,  Yulia V Surovtseva  2 ,  Brett D Lindenbach  3 ,  Junjie U Guo  1
Affiliations
  • 1. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
  • 2. Yale Center for Molecular Discovery, Yale University, West Haven, CT, USA.
  • 3. Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
PMID: 33106809 DOI: 10.1101/2020.10.21.349225
Abstract

Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires programmed -1 ribosomal frameshifting (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone Antibacterial, as a -1 PRF inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of Other beta coronaviruses. Importantly, frameshift inhibition by merafloxacin substantially impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing the proof of principle of targeting -1 PRF as an effective Antiviral strategy for SARS-CoV-2.

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