Transcription Regulatory Sequences in Coronaviruses: Mechanistic Foundations for Antivirals and Vaccines

-acting signals that direct polymerase pausing and template switching during negative-strand synthesis. The COVID-19 pandemic spurred intensive investigation of SARS-CoV-2 gene expression, yielding high-resolution transcriptome maps, genome-wide RNA structure data, and detailed structural models of the replication-transcription complex (RTC). TRS function is therefore best understood as a multi-scale property determined not by the core motif alone, but by the integration of primary-sequence complementarity, local RNA secondary structure, long-range RNA-RNA interactions, and RTC dynamics. This review provides an integrated view of TRS structure-function relationships, with emphasis on how these features collectively shape sgRNA abundance, junction diversity, recombination potential, and prospects for diagnostic and antiviral applications, including vaccines and therapeutics.