NACE2i

NACE2i is a cell permeable, specific and selective peptide inhibitor of nuclear ACE2, inhibits binding between IMP1α and ACE2 and SARS-CoV-2 viral replication. NACE2i specifically targets nuclear ACE2 and not other nuclear proteins targeted by the importin pathway. NACE2i has no impact on ACE2 enzymatic activity. NACE2i prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages. NACE2i has a dual mode of action: suppressing the lethal inflammation in severe COVID-19 and inhibiting viral replication by restoring host translation of anti-viral cytokines.