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. 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 .