Involvement of 5' and 3' UTRs on SARS-CoV-2 Genome Packaging

Abstract

The SARS-CoV-2 virus, responsible for the COVID-19 pandemic, packages its large single-stranded RNA genome through a precise yet enigmatic mechanism. A packaging signal (PS) within its genome was proposed to facilitate the assembly of new viral particles. Here in this study, we report the role of the 5 and 3 untranslated regions (UTRs) in PS-mediated genome packaging. Utilizing proximity ligation data, we demonstrate direct interactions between the UTRs and the PS9 element, a key packaging signal within the SARS-CoV-2 genome. Multiple evidence confirmed that the presence of UTRs enhance the packaging efficiency of infectious virus-like particles (iVLPs) and recruits more nucleocapsid (N) protein, suggesting a critical role in genome compaction and packaging. These insights into the regulatory mechanisms of SARS-CoV-2 genome packaging provide novel targets for antiviral therapeutics and contribute to the broader understanding of coronavirus assembly.