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• W3086435500 abstract "SARS-CoV-2 uses −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins. Because modulating −1 PRF can attenuate the virus, ligands binding to the RNA pseudoknot that stimulates −1 PRF may have therapeutic potential. Mutations in the pseudoknot have occurred during the pandemic, but how they affect −1 PRF efficiency and ligand activity is unknown. Studying a panel of six mutations in key regions of the pseudoknot, we found that most did not change −1 PRF levels, even when base-pairing was disrupted, but one led to a striking 3-fold decrease, suggesting SARS-CoV-2 may be less sensitive to −1 PRF modulation than expected. Examining the effects of a small-molecule −1 PRF inhibitor active against SARS-CoV-2, it had a similar effect on all mutants tested, regardless of basal −1 PRF efficiency, indicating that anti-frameshifting activity can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of −1 PRF." @default.
• W3086435500 created "2020-09-21" @default.
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• W3086435500 date "2020-10-01" @default.
• W3086435500 modified "2023-10-17" @default.
• W3086435500 title "Anti-Frameshifting Ligand Active against SARS Coronavirus-2 Is Resistant to Natural Mutations of the Frameshift-Stimulatory Pseudoknot" @default.
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• W3086435500 doi "https://doi.org/10.1016/j.jmb.2020.09.006" @default.
• W3086435500 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7483078" @default.
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