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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Proc+Natl+Acad+Sci+U+S+A 2021 ; 118 (26): ä Nephropedia Template TP
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Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting #MMPMID34185680
Sun Y; Abriola L; Niederer RO; Pedersen SF; Alfajaro MM; Silva Monteiro V; Wilen CB; Ho YC; Gilbert WV; Surovtseva YV; Lindenbach BD; Guo JU
Proc Natl Acad Sci U S A 2021[Jun]; 118 (26): ä PMID34185680show ga
Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses. Consistent with the essential role of -1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting -1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses.