Role of Top1 and Genome structure in SARS-CoV-2 infection [RNA-Seq hamster]

The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Targeting these pathways might therefore be a viable therapeutic strategy. Previously, we have reported that chromatin factors such as Topoisomerase I (Top1) play key roles in controlling the induction of inflammatory gene expression programs. Here, by using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we show that Topoisomerase 1 (Top1) inhibition in infected cells and animals suppresses lethal inflammation induced by SARS-CoV-2. Overall design: To study the role of Top1 in modulating inflammation during SARS-CoV-2 in vivo, we infected golden syrian hamsters with SARS-CoV-2. Animals were dosed with either 10mg/kg TPT or vehicle control alone (DMSO) at Days 1 and 2 post infection. Thereafter, lungs of animals were collected at either day4 or day 6 post infection. All conditions were done with 3 animals (3 biological replicates).