Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression
In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5' region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.PMID:37563335 | DOI:10.1007/s12272-023-01458-x
Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Maria Razzaq Ji Ho Han Subramaniyam Ravichandran Jaehyun Kim Joon-Yong Bae Man-Seong Park Shrute Kannappan Woo-Chang Chung Jin-Hyun Ahn Moon Jung Song Kyeong Kyu Kim Source Type: research
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