The research team found the coronavirus can't evade the ACE2 receptor decoy because mutations in the virus that would allow it to avoid the drug, DF-COV-01, would also lower the virus's ability to infect cells (Science Advances, December 7, 2022).

ACE2 decoys are effective against the COVID-19 virus because they trigger an irreversible change in the structure of the virus; the top of the viral spike protein gets "popped off" so it can't bind to the cell-surface ACE2 receptor and infect cells.

The decoys lure the virus to bind to the decoy instead of the cell, lop off the spike, and inactivate the virus before it can enter cells. Also, when the researchers included a piece of the ACE2 protein, the collectrin-like domain, it made DF-COV-01 stick more tightly to the virus and had a longer life in the body of animals used in the study.

Binding to ACE2 is required for infection so variants can change but they must continue to bind to ACE2 and the ACE2 decoy makes the drug persistently active against all variants. That means the drug could be useful to treat new coronaviruses that might emerge in the future, the researchers said.

The drug hasn't been tested in humans yet. However, manufacturing development is nearly completed and preclinical studies needed for regulatory approval are underway, the team added.