Decoy receptors could prevent and treat COVID-19 infection while minimizing the risk of escape variants, according to preclinical research recently published in PNAS.
The evolution of SARS-CoV-2 has made monoclonal antibodies that target the spike protein of the virus less effective, eliminating some of the tools that physicians had to treat and prevent infection. Scientists at New York University Grossman School of Medicine identified receptor decoys as an alternative approach that is less vulnerable to viral evolution.
Rather than target the viral protein, the researchers proposed introducing a decoy version of the ACE2 protein that SARS-CoV-2 binds to when entering cells. Viruses that bind to the decoy cannot enter cells to replicate. Because the virus can only replicate if it can bind to ACE2, the scientists speculated that the pathogen cannot easily evolve to avoid the decoy receptors.
To test that idea, the researchers used a viral vector to deliver the genetic code for an ACE2 decoy in mice. Other papers, including one by the Grossman scientists, have described the use of decoy receptors; however, using a viral vector to get the body to produce ACE2, rather than administering the protein directly, could provide more durable protection.
In mice, the lentiviral vector-based decoy provided protection from infection for at least two months. The level of protection was unchanged at the end of the two-month study. However, the durability of protection provided by candidates that used adeno-associated virus (AAV) vectors was limited. There is more safety data on the use of AAVs than lentiviruses in humans.
