Untangling the pseudoknots of SARS-CoV-2: Insights into structural heterogeneity and plasticity

Since the onset of the COVID-19 pandemic, one productive area of research has focused on the intricate two- and three-dimensional structures taken on by SARS-CoV-2's RNA genome. These structures control essential viral processes, making them tempting targets for therapeutic intervention. This review focuses on two such structured regions, the frameshift stimulation element (FSE), which controls the translation of viral protein, and the 3′ untranslated region (3′ UTR), which is thought to regulate genome replication. For the FSE, we discuss its canonical pseudoknot's threaded and unthreaded topologies, as well as the diversity of competing two-dimensional structures formed by local and long-distance base pairing. For the 3′ UTR, we review the evidence both for and against the formation of its replication-enabling pseudoknot.