Interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses SARS coronavirus replication

Dae Gyun Ahn, Wooseong Lee, Jin Kyu Choi, Seong Jun Kim, Ewan P. Plant, Fernando Almazán, Deborah R. Taylor, Luis Enjuanes, Jong Won Oh

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The programmed -1 ribosomal frameshifting (-1 PRF) utilized by eukaryotic RNA viruses plays a crucial role for the controlled, limited synthesis of viral RNA replicase polyproteins required for genome replication. The viral RNA replicase polyproteins of severe acute respiratory syndrome coronavirus (SARS-CoV) are encoded by the two overlapping open reading frames 1a and 1b, which are connected by a -1 PRF signal. We evaluated the antiviral effects of antisense peptide nucleic acids (PNAs) targeting a highly conserved RNA sequence on the - PRF signal. The ribosomal frameshifting was inhibited by the PNA, which bound sequence-specifically a pseudoknot structure in the -1 PRF signal, in cell lines as assessed using a dual luciferase-based reporter plasmid containing the -1 PRF signal. Treatment of cells, which were transfected with a SARS-CoV-replicon expressing firefly luciferase, with the PNA fused to a cell-penetrating peptide (CPP) resulted in suppression of the replication of the SARS-CoV replicon, with a 50% inhibitory concentration of 4.4. μM. There was no induction of type I interferon responses by PNA treatment, suggesting that the effect of PNA is not due to innate immune responses. Our results demonstrate that -1 PRF, critical for SARS-CoV viral replication, can be inhibited by CPP-PNA, providing an effective antisense strategy for blocking -1 PRF signals.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalAntiviral Research
Volume91
Issue number1
DOIs
Publication statusPublished - 2011 Jul

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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