Xing Wang and team develop new method of COVID prevention

While the COVID pandemic may be behind us, the transmission and mutations of the virus have continued, making it difficult to keep the disease and its variations under control. In an exciting development towards coronavirus containment, Professor Xing Wang and his team, including virology collaborator Professor Lijun Rong at the College of Medicine (UIC), have created a polyvalent nanobody structure (or “PNS”) that shows the potential to effectively prevent SARS-CoV-2 and other viral infections. This research has been published in the Journal of the American Chemical Society, and can be read online here. 

PNS is created by combining single-stranded DNA and nanobodies at a selective site, and is then attached to a gold nanoparticle. This creates a structure that matches the spatial pattern of the trimeric spike protein on SARS-CoV-2’s surface. 

The SARS-CoV-2 virus itself infects ​​its host by using a spike protein to bind to human cells; PNS disrupts this process by binding to the virus. It does this roughly 1,000 times more effectively than individual nanobodies, meaning it can intercept and prevent viruses from attaching to healthy cells at a much higher rate.

Wang and his team saw the need for an alternative method of virus containment after identifying an existing need in the way these viruses are traditionally treated. 

“Neutralizing antibodies are effective therapeutics for combating virus infections,” said Wang. “However, producing these antibodies for therapeutics is very costly and time-consuming. Antibodies are also not stable for storage and transportation in ambient conditions.”

Nanobodies, derived from an antibody's heavy-chain, are known for their remarkable stability even in challenging conditions. They can also be produced cost-effectively using bacteria. Despite these advantages, individual nanobodies are much less potent compared to therapeutic antibodies, and are hundreds of times less effective.

Their PNS solution addresses these issues while also managing a higher virus interception rate than other nanobody-based solutions. The result is an effective way to block virus-host cell interactions.

This exciting discovery builds upon previous research conducted in the Wang lab; a key part of the PNS development process involved utilizing the multivalency + pattern-matching strategy previously established by Wang’s group. This strategy uses spatial pattern-matching with SARS-CoV-2 spike proteins to make highly effective binding possible, and is the basis of this most recent research.

This newest discovery shows that the Wang lab’s multivalency + pattern-matching strategy has the ability to convert less effective antiviral reagents quickly and conveniently to potent viral inhibitors with a short turnaround time.tinjie

Wang and his team are optimistic about what these findings mean for not only future SARS-CoV-2 treatments, but other diseases as well.

“We foresee that our PNS can be formulated as a nasal spray and applied as a preventive reagent to bind airborne respiratory viruses such as SARS-CoV-2 and influenza,” said Wang. “Additionally, our PNS can be systematically administered as a therapeutic reagent to capture and neutralize target viruses like HIV in blood circulation.”

Wang believes that the theory behind PNS could expand even farther, to assist in targeted delivery to immune cells by utilizing engineered nanobodies for immunotherapy.

Wang expressed gratitude for the hard work of his team members, as well as the collaborative environment that led to these findings. 

“The study was led by the excellent fellows Tingjie Song (UIUC) and Laura Cooper (UIC), which is one of the ongoing and exciting UIUC-UIC collaborative projects aiming to advance infection disease therapy and diagnosis technologies,” Wang said. 

Read their published research here.