Early in the COVID-19 pandemic, monoclonal antibodies played an important role in treating some people with severe disease. A combination of antibodies was also approved as a prevention strategy for people with certain immune system problems.
As the SARS-CoV-2 virus continues to mutate, the spike protein it uses to enter human cells has changed substantially. Because of this, the monoclonal antibodies designed to bind earlier versions of the spike have become ineffective over time. Researchers have been searching for new ways to combat COVID-19 in people with a compromised immune response.
A research team from NYU Langone Health led by Dr. Nathaniel Landau developed a type of molecular decoy designed to tie up the virus in the body before it can enter human cells. The decoy includes a version of human ACE2, the protein that SARS-CoV-2 latches onto to enter cells. Since the virus needs to bind ACE2 in order to enter cells, the researchers reasoned that this aspect of the virus’s function, and therefore structure, is unlikely to change much.
The team fused ACE2 to a piece of antibody that helps the immune system attack the virus and clear it from the body. A harmless version of a virus called AAV was engineered to carry the gene for the decoy. The virus could then infect cells and instruct them to produce copies of the decoy. The team tested this new decoy in cells and in mice. Their results were published on June 6, 2023, in the Proceedings of the National Academy of Sciences.