Researchers at North Carolina State University have developed a nanodecoy system that provides binding sites for the SARS-CoV-2 virus. The vesicles help to prevent the virus from binding to lung cells and lead to its eventual destruction by the immune system. The nanodecoys are derived from lung spheroid cells, and contain the angiotensin-converting enzyme 2 (ACE2) receptor on their surface. The ACE2 receptor is the binding site and entry point for the SARS-CoV-2 virus into lung cells, so the vesicles essentially act as fake binding sites, tricking the virus. The nanodecoys have shown promise as an inhaled treatment in rodents and non-human primates, and may be useful as a COVID-19 treatment in humans.
Existing approaches to fighting the SARS-CoV-2 virus have mostly focused on the virus itself. All our vaccines are targeted against the spike protein, and one of the few approved direct treatments for COVID-19 (rather than treatments to deal with symptoms) are monoclonal antibodies targeted against the virus. However, as the new viral variants have shown, the virus is not a static target, and such treatments could be rendered ineffective by viral mutations.
What is less likely to change is the viral target within our body – the ACE2 receptor. This latest treatment aims to overwhelm the viral particles in the lungs with binding sites, rendering it ineffective and easily cleared by the immune system. The researchers hope that the treatment could enhance viral clearance from the body, reduce symptoms, and stop the virus from damaging our lungs.
“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,” explained Ke Cheng, a researcher involved in the study, in a North Carolina State University press release. “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.”
So far, the researchers have shown that the inhaled nanodecoys stick around in the lungs in mice for at least 72 hours, and increase the clearance of a virus that mimics SARS-CoV-2. Another study in macaques showed that the nanodecoys reduced lung inflammation and fibrosis and increased viral clearance. Further work is required to gauge the potential of the treatment for human patients.
“By focusing on the body’s defenses rather than a virus that will keep mutating we have the potential to create a therapy that will be useful long-term,” said Cheng. “As long as the virus needs to enter the lung cell, we can keep tricking it.”
Here’s an explanatory video from North Carolina State about the new technology:
Study in Nature Nanotechnology: Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19