The emergence of new SARS-CoV-2 variants constantly challenges existing COVID-19 vaccines and therapies. While vaccines effectively prevent severe illness, breakthrough infections pose a threat to vulnerable populations, especially older adults and immunocompromised individuals. 

A team of researchers at the University of Michigan led by chemical engineer Nicholas Kotov and Jiangnan University immunologist Chuanlai Xu, designed a teardrop-shaped nanoparticle that inactivated a wide range of SARS-CoV-2 variants. The research, published in Proceedings of the National Academy of Sciences, offered a potentially broad-spectrum therapeutic approach for COVID-19 (1).

“This work is to find new methods to combat viruses,” explained Kotov, a coauthor of the study. “One of the big problems that we all need to be conscious about [is that] this is not the last pandemic. It might be the same coronavirus. It might be another virus; and we must have an arsenal.”

Current treatment options for COVID-19 are limited. Antiviral drugs like Paxlovid show promise, but their efficacy can vary depending on the viral strain and patient factors (2). Paxlovid works by inhibiting a crucial enzyme that the viral variant needs to make copies of itself, essentially disrupting the internal mechanisms of the virus.  

Kotov and his team wanted to go a step further and design a molecule that could act as a first line of viral defense, a molecule that could effectively incapacitate the virus independent of strain in a therapeutic method not currently used. They decided to target a core feature of the SARS-CoV-2 virus: the spike protein. This protein acts like a key, unlocking human cells for viral entry. Existing vaccines target specific regions of the spike protein, but mutations can render these regions unrecognizable, allowing new variants to evade immunity.

The researchers crafted nanoparticles with a tapered, teardrop shape and a left-handed twist, mirroring the chirality, or "handedness," of the viral spike protein. This design allowed for a snug fit between the nanoparticle and the viral protein, blocking the key and preventing viral entry. With no payload or delivery, these particles cover the virus completely, effectively smothering it. Unlike current antiviral therapeutic molecules, these nanoparticles are thermally stable at room temperature, which is ideal for healthcare settings with limited resources. 

“This shape was just amazing,” said Guilin Wang, a nanoparticle researcher from the University of Crete, who did not participate in the study. “It's important because we see that the largest activity binds using the tip, the pointy part of the nanoparticle, but not the blunt part.” 

The researchers tested their creation against various strains, including the common cold viruses and the SARS-CoV-2 strains Wuhan-1 and the Omicron variant. In a preclinical model using mice infected with pseudoviruses mimicking different strains, treatment with inhaled nanoparticles resulted in a 95 percent reduction in viral load within the lungs. The treatment also offered protection against subsequent infection for up to three days.

This opens an enormous area in medicine. This is a fine design that is typical for biomolecules. I would like to translate it to nanoparticles. 
- Nicholas Kotov, University of Michigan

“It’s quite inspiring because we can potentially use this as a fairly reliable first option,” said Kotov. “It may work. It may not. But if somebody is facing a room full of dying people and they need to help, at least it would provide some degree of protection.”

While these results are encouraging, further research is needed. The researchers want to determine how easily the virus develops resistance to these nanoparticles. Continued investigation of safety and delivery methods could pave the way for a valuable tool in the ongoing fight against the pandemic. “This opens an enormous area in medicine,” said Kotov. “This is a fine design that is typical for biomolecules. I would like to translate it to nanoparticles.”

References

1. Gao, R. et al. Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants. PNAS  121, e2310469121 (2024).
2. Najjar-Debbiny, R. et al. Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients. Clin Infect Dis  76, e342–e349 (2023).