Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting

Proc Natl Acad Sci U S A. 2021 Jun 29;118(26):e2023051118. doi: 10.1073/pnas.2023051118.


Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-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 for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses. Consistent with the essential role of -1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting -1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses.

Keywords: RNA pseudoknot; coronavirus; merafloxacin; ribosomal frameshifting; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Betacoronavirus
  • Chlorocebus aethiops
  • Fluoroquinolones / pharmacology
  • Frameshifting, Ribosomal / drug effects*
  • Frameshifting, Ribosomal / genetics
  • Mutation
  • Nucleic Acid Conformation
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / physiology
  • Vero Cells
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Fluoroquinolones
  • RNA, Viral
  • CI 934