Coronaviral frameshifting stimulation element RNA pseudoknot (FSE pseudoknot)

The **coronaviral frameshifting stimulation element (FSE) RNA pseudoknot** is a structured RNA element present in all known coronaviruses, including SARS-CoV-2, within the viral genomic RNA. It is located downstream of a conserved heptanucleotide “slippery site” and is essential for mediating programmed -1 ribosomal frameshifting (-1 PRF), through which viral polyproteins (notably the RNA-dependent RNA polymerase and its cofactors) are synthesized[1][7]. The FSE typically forms a complex three-stem pseudoknot (H-type), though it may adopt multiple alternative folds depending on sequence context and length, reflecting its structural plasticity[2][3][6]. The correct folding and dynamic transitions of the pseudoknot are critical for viral fitness as they regulate the efficiency of frameshifting and ultimately the stoichiometry of viral proteins[1][2][3][6][7]. Because of its functional conservation and structural necessity, the FSE pseudoknot represents a validated and promising target for antiviral drug development, with several classes of small molecules and antisense oligonucleotides reported to bind specifically to this RNA structure and disrupt or modulate frameshifting, thereby inhibiting viral replication[4][6][7].

Other names

coronavirus frameshift element pseudoknot-1 programmed ribosomal frameshift pseudoknotSARS-CoV-2 FSE RNA pseudoknot

Small molecules bind to the pseudoknot structure, stabilize or alter its conformation, thereby inhibiting or modulating frameshifting efficiency and reducing viral protein synthesis[4][7] Antisense oligonucleotides that disrupt or alter the FSE pseudoknot reduce frameshifting and viral replication[6]