The frameshifting element in coronaviruses: structure, function, and potential as a therapeutic target.

The frameshifting element (FSE) comprises a slippery heptanucleotide sequence followed by a downstream RNA structure, such as a pseudoknot or stem-loop. Found in various RNA viruses, FSE regulates viral replication via programmed -1 ribosomal frameshifting (-1 PRF), making it a potential broad-spectrum antiviral target. Advances in RNA structural analysis have elucidated the dynamic conformations and cross-viral diversity of FSE, with the SARS-CoV-2 outbreak further highlighting its role in viral replication. Efforts to develop antiviral drugs targeting FSE have progressed through virtual and phenotypic screening. In this review, we explore the evolution, structure, and function of FSE in coronaviruses, evaluate recent advances in FSE-targeted drug development, and discuss their design advantages, efficacy, and challenges, providing insights for future antiviral strategies.