Omicron variant of SARS-CoV-2 exhibits an increased resilience to the antiviral type I interferon response (preprint)

The new variant of concern (VOC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Omicron (B.1.1.529), is genetically very different from other VOCs. We compared Omicron with the preceding VOC Delta (B.1.617.2) and the wildtype strain (B.1) with respect to their interactions with the antiviral type I interferon (IFN-alpha/beta) response in infected cells. Our data indicate that Omicron has gained an elevated capability to suppress IFN induction upon infection and to better withstand the antiviral state imposed by exogenously added IFN-alpha.

The short and long-range RNA-RNA Interactome of SARS-CoV-2 (preprint)

The Coronaviridae are a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and its subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome adopts alternative topologies inside cells and undergoes genome cyclization. In addition, the SARS-CoV-2 genome and subgenomic mRNAs engage in different interactions with host RNAs. Most importantly, we discovered a long-range RNA-RNA interaction - the FSE-arch - that encircles the programmed ribosomal frame-shifting element. The FSE-arch is conserved in the related MERS-CoV virus and is under purifying selection. Our findings illuminate RNA-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses, and will aid future efforts to develop antiviral strategies.