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Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting

Yu Sun, Laura Abriola, Rachel O. Niederer and 9 more

Proceedings of the National Academy of Sciences · 2021 · CC BY

doi:10.1073/pnas.2023051118

Abstract

Significance A large variety of RNA viruses, including the novel coronavirus SARS-CoV-2, contain specific RNA structures that promote programmed ribosomal frameshifting (PRF) to regulate viral gene expression. From a high-throughput compound screen, we identified a PRF inhibitor for SARS-CoV-2 and found that it substantially impeded viral replication in cultured cells. Interestingly, the compound could target not only SARS-CoV-2 but also other coronaviruses that use similar RNA structures to promote frameshifting. These results suggest targeting PRF is a plausible, effective, and broad-spectrum antiviral strategy for SARS-CoV-2 and other coronaviruses.

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