Nanodecoy therapy binds and neutralizes SARS-CoV-2 virus

Nanodecoys made from human lung spheroid cells (LSCs) can bind to and neutralize SARS-CoV-2, promoting viral clearance and reducing lung injury in a macaque model of COVID-19.

By mimicking the receptor that the virus binds to rather than targeting the virus itself, nanodecoy therapy could remain effective against emerging variants of the virus.

SARS-CoV-2 enters a cell when its spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell's surface. LSCs – a natural mixture of lung epithelial stem cells and mesenchymal cells – also express ACE2, making them a perfect vehicle for tricking the virus.

"If you think of the spike protein as a key and the cell's ACE2 receptor as a lock, then what we are doing with the nanodecoys is overwhelming the virus with fake locks so that it cannot find the ones that let it enter lung cells," says Ke Cheng, corresponding author of the research. "The fake locks bind and trap the virus, preventing it from infecting cells and replicating, and the body's immune system takes care of the rest."

These nanodecoys are essentially cell 'ghosts,' and one LSC can generate around 11,000 of them," Cheng says. "Deploying millions of these decoys exponentially increases the surface area of fake binding sites for trapping the virus, and their small size basically turns them into little bite-sized snacks for macrophages, so they are cleared very efficiently."