Open AccessRestriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Author(s) -
Yu Sun,
Laura Abriola,
Rachel O. Niederer,
Savannah F. Pedersen,
Mia Madel Alfajaro,
Valter Silva Monteiro,
Craig B. Wilen,
Ya Chi Ho,
Wendy V. Gilbert,
Yulia V. Surovtseva,
Brett D. Lindenbach,
Junjie U. Guo
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2023051118
Subject(s) - translational frameshift , biology , virology , viral replication , rna , coronavirus , gene , covid-19 , ribosome , genetics , virus , medicine , disease , pathology , infectious disease (medical specialty)
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.