Figure 1.

A decoy angiotensin-converting enzyme 2 (ACE2) receptor mutant, sACE2₂.v2.4-IgG1, prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake by lung epithelial cells and ameliorates lung injury caused by SARS-CoV-2 infection in mice expressing human ACE2 (hACE2).

SARS-CoV-2 in the pulmonary airways and alveolar airspaces binds wild type (WT) hACE2 expressed on the surface of epithelial cells to gain entry and initiate an infection, leading to lung epithelial and endothelial injury that culminates in lung edema, alveolar-capillary hyperpermeability, and mortality characterizing coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) in patients. A soluble decoy ACE2 receptor mutant, sACE2₂.v2.4-IgG1, competitively binds SARS-CoV-2 spike protein with greater affinity than WT hACE2 and prevents viral uptake by lung epithelial cells. In K18-hACE2 mice expressing WT hACE2 on the lung epithelium and infected with SARS-CoV-2, intravenously infused sACE2₂.v2.4-IgG1 fusion protein achieves stable concentration in the lungs and reduces lung edema and lung viral load, returns alveolar-capillary barrier permeability to a more normal level, and improves survival.