Study Points to SARS-CoV-2 Protection by Peptide Inhibitor Preventing Receptor Translocation

In Nature Communications, researchers at QIMR Berghofer Medical Research Institute, the University of Paris-Saclay, and elsewhere describe a "protective epigenetic scarring of ACE2" approach for dialing down SARS-CoV-2-related effects by interfering with ACE2 receptor translocation from the cell membrane to the nucleus. With lung tissue experiments in golden Syrian hamsters infected with SARS-CoV-2, the team narrowed in on a peptide that inhibits nuclear translocation of ACE2, leading to reduced replication of the coronavirus. Through a series of follow-up experiments, the authors showed that this inhibitor was linked to lower-than-usual inflammation and enhanced natural killer cell infiltration, along with altered ACE2 methylation and other immune-related changes in the animal's lung cells after SARS-CoV-2 infection. These and other results suggest that nuclear ACE2 "may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry," they suggest, adding that "therapeutics are undoubtedly required in combination with vaccines to enhance and prolong protection" against SARS-CoV-2 variants.