Authors
Jiajing Guo, Mengqi Yu, Yue Sun, Qiao Chen, Fei Liu, Yanke Shan
Published in
Transboundary and emerging diseases. Volume 2026. Issue 1. Pages e5088147.
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that poses a considerable risk to swine production worldwide. G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures known to regulate critical steps of viral life cycles in multiple viruses; however, the existence and biological role of RNA G4s (RG4s) in PDCoV remain unclear. In this study, we identified putative G4-forming sequences (PQSs) in the nonstructural proteins 2 (Nsp2) and M genes of the PDCoV genome, which are highly conserved across PDCoV strains, based on bioinformatic analysis. Fluorescence turn-on assays and circular dichroism (CD) spectroscopy revealed that these PQSs fold into typical parallel RG4 structures in vitro, and their RG4 formation in living cells was further confirmed using G4-specific probes. Notably, treatment with the G4 ligands TMPyP4 and pyridostatin (PDS) significantly reduced PDCoV N mRNA abundance and corresponding protein expression, concomitant with a marked decrease in viral titers in LLC-PK1 cells. In addition, RG4 structures identified in the Nsp2 and M mRNAs were shown to inhibit translation through a posttranscriptional mechanism. Moreover, G4 ligands, such as PDS and TMPyP4, targeted the RG4 structure in Nsp2 mRNA and significantly inhibited Nsp2-EGFP fusion protein expression without affecting the expression of the M-EGFP fusion protein. In summary, our work supports the presence of sequence-conserved functional RG4 structures in the PDCoV genome and provides new insights into the development of antiviral strategies targeting PDCoV RG4s.
PMID:
42536048
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.
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