In vivo inhibition of nuclear ACE2 translocation protects against SARS-CoV-2 replication and lung damage through epigenetic imprinting

In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. NACE2i also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment restores host translation in infected hamster bronchiolar cells. Overall design: Comparative gene expression profiling analysis of spatial RNA-seq data for the selected regions of interest (ROIs) on the lung tissues of SARS-CoV-2 infected hamster with or without NACE2i treatment .