The surface protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as the spike protein, is critical for infecting host cells. The spike protein facilitates the infection process by binding to angiotensin-converting enzyme 2 (ACE2) receptors on the surface of airway epithelial cells, initiating the virus entry into the cells.
, researchers demonstrated a novel method to neutralize the virus effectively. The engineered ACE2 acts as a decoy by binding to the viral spike protein, thus preventing the binding of viruses to the ACE2 receptor on the cell surface. This inhibition by the ACE2 decoy is detrimental to SARS-CoV-2.
Engineered ACE2 decoy with high affinity and an IgG1 Fc domain demonstrated potent neutralization against Omicron subvariants, including emerging strains. The ability to prevent escape mutants and display therapeutic activity in a primate model was demonstrated for the first time, which suggests its potential as a promising strategy against immune-evading SARS-CoV-2 variants.
Further, the team tested the feasibility of the 3N39v4-Fc administration via the inhalation route, as compared with the administration via the intravenous injection route used in the team's earlier study. imaging and zirconium -labeling, the team found that the distribution and clearance patterns within the body differed between inhalation and intravenous administration route in rodents.
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