| Literature DB >> 34185680 |
Yu Sun1, Laura Abriola2, Rachel O Niederer3, Savannah F Pedersen4, Mia M Alfajaro5,6, Valter Silva Monteiro6, Craig B Wilen5,6, Ya-Chi Ho4, Wendy V Gilbert3, Yulia V Surovtseva2, Brett D Lindenbach7, Junjie U Guo8.
Abstract
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.Entities:
Keywords: RNA pseudoknot; coronavirus; merafloxacin; ribosomal frameshifting; translation
Year: 2021 PMID： 34185680 DOI： 10.1073/pnas.2023051118
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205