期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 231, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2023.123282
关键词
Porcine epidemic diarrhea virus; G-quadruplex; Antiviral activity
Porcine epidemic diarrhea virus (PEDV) is a significant threat to the global pig industry, but there is a lack of accurate targets for anti-PEDV drugs. This study identified G-quadruplex structures in the PEDV genome and showed that G4-specific compounds can inhibit the virus at the replication and protein expression stages. These findings provide new insights into developing antiviral drugs targeting PEDV RNA G-quadruplexes.
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there are still no anti-PEDV drugs with accurate targets. G-quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA, and have attracted great attention as potential targets for antiviral strategy. In this study, we reported two putative G4-forming sequences (PQS) in S and Nsp5 genes of PEDV genome based on bioinformatic analysis, and identified that S-PQS and Nsp5-PQS were enabled to fold into G4 structure by using circular dichroism spectroscopy and fluorescence turn-on assay. Furthermore, we verified that both S-PQS and Nsp5-PQS PQS could form G4 structure in live cells by immunofluorescence microscopy. In addition, G4-specific compounds, such as TMPyP4 and PDS, could signifi-cantly inhibit transcription, translation and proliferation of PEDV in vitro. Importantly, these compounds exert antiviral activity at the post-entry step of PEDV infection cycle, by inhibiting viral genome replication and protein expression. Lastly, we demonstrated that TMPyP4 can inhibit reporter gene expression by targeting G4 structure in Nsp5. Taken together, these findings not only reinforce the presence of viral G-quadruplex sequences in PEDV genome but also provide new insights into developing novel antiviral drugs targeting PEDV RNA G-quadruplexes.
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