Decoy Nanoparticles Mimic Cells to Combat COVID-19, Here’s How It Works

As the ever-evolving COVID-19 virus starts evading once-promising therapeutics such as monoclonal antibody treatments, scientists have turned more interested in the "decoy" nanoparticles.

As described in a EurekAlert! report, the said nanoparticles might look like cells and function like such. However, a new potential treatment for the virus is a "cleverly disguised trickster," attracting viruses, binding them, and rendering them inactive. Replicating regular cells, decoy nanoparticles are soaking up viruses like a sponge, hindering them from infecting the rest of the body.

In new research, synthetic biologists have set out to elucidate the design rules required to make decoy nanoparticles effective, not to mention resistant to viral leaks.

Decoy Nanoparticles

After designing and testing different iterations, the scientists identified a broad set of decoys, all "manufacturable" using different methods, that were incredibly efficient against the original virus and mutant variants.

In fact, decoy nanoparticles were up to 50 times more efficient in hindering naturally occurring viral mutants than customary, protein-based inhibitor drugs.

When tested against a viral mutant developed to resistant like treatments, decoy nanoparticles were up to 1,500 times more effective at blocking infection.

Even though much more studies and clinical evaluations are needed, the study investigators believe decoy nanoparticle infusions someday could be used to treat patients with severe or prolonged viral infections.

Efficacy Against COVID-19 Variants

In the study, published in the Small journal, the research team tested decoy nanoparticles against the parent SARS-CoV-2 virus and five COVID-19 variants including delta, beta, lambda, and delta-plus, in cellular culture.

According to Joshua Leonard of Northwestern University, the study's co-senior author, they showed that decoy nanoparticles are effective inhibitors of all the different viral variants. He added even strains that escape other drugs did not leak out from decoy nanoparticles.

Neha Kamat, also from Northwestern and co-senior author of the study, said that different strains kept popping up around the world as they were performing the research. She added, that they kept testing the decoys against the new strains, and they just kept being effective. As the SARS-CoV-2 virus has mutated to develop new strains, some treatments have turned less effective in combating the ever-evolving virus.

COVID-19 Infecting Human Cells

A month ago, the United States Food and Drug Administration paused numerous monoclonal antibody treatments, for instance, because of their failure against the COVID-19 BA.2 omicron sub-variant.

Nevertheless, even where treatments were unsuccessful, the decoy nanoparticles in the new study never lost their efficacy. According to Leonard, this is due to the fact that decoys put SAR-CoV-2 between an evolutionary rock and a hard place.

Essentially, SARS-CoV-2 is infecting human cells by binding its infamous spike protein to the human angiotensin-converting enzyme 2 or ACE2 receptor. A protein on the cells' surface, ACE2 offers an entry point of the virus.

ACE2 Receptors Overexpressed

The Northwestern team used nanosized particles or extracellular vesicles to be able to design nanoparticles, naturally released from all types of cells. As indicated in a similar ScienceDaily report, they engineered cells that produce such particles to overexpress the gene for ACE2, resulting in many ACE2 receptors on the surfaces of particles.

When SARS-CoV-2 came into contact with the decoy, it tightly bonded to the said receptors instead of real cells, rendering the virus failing to infect cells.

Leonard explained that it needs to bind to the ACE2 receptor for the virus to enter the cell. He added decoy nanoparticles present an evolutionary challenge for the COVID-19 virus.

It would need to develop a different way to penetrate the cells to avoid the need to use ACE2 receptors. There is no evident evolutionary escape route.

Exhibiting Low Toxicity

On top of being effective against drug-resistant viruses, decoy nanoparticles are coming with many other benefits. Since they are biological instead of synthetic materials, the nanoparticles are less possible to elicit an immune response which causes inflammation and can interfere with the efficacy of the drug.

They show low toxicity as well, making them specifically well-suited for use in sustained or repeated administration for the treatment of seriously ill patients.

When the COVID-19 pandemic started, scientists and clinicians experienced an unnerving gap between detecting the virus and developing new drugs for the virus's treatment.

For the next pandemic, decoy nanoparticles could offer a quick, effective treatment prior to the development of the vaccine.

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