DNA nets effectively target the spike protein and detect the COVID-19 virus at very low levels

Tiny nets woven from strands of DNA can entangle the spike protein of the virus that causes COVID-19, illuminating the virus for a quick but sensitive diagnostic test — as well as preventing the virus from infecting cells, causing a new possible route to antiviral drugs is opened. treatment, according to a new study.

Researchers at the University of Illinois Urbana-Champaign and collaborators demonstrated the DNA nets’ ability to detect and inhibit COVID-19 in human cell cultures in a paper published in the Journal of the American Chemical Society.

“This platform combines the sensitivity of PCR with the speed and low cost of antigen testing,” said study leader Xing Wang, a professor of bioengineering and chemistry in Illinois. “We need tests like this for a number of reasons. One is to prepare for the next pandemic. The other reason is to monitor the ongoing viral epidemics – not just coronaviruses, but other deadly and economically impactful ones.” viruses such as HIV or the flu.”

DNA is best known for its genetic properties, but it can also be folded into modified nanoscale structures that can perform functions or bind specifically to other structures, much like proteins do. The DNA nets the Illinois group developed were designed to bind to the coronavirus spike protein — the structure that protrudes from the surface of the virus and binds to receptors on human cells to infect them. Once bound, the nets emit a fluorescent signal that can be read by an inexpensive handheld device in about 10 minutes.

The researchers showed that their DNA nets effectively targeted the spike protein and were able to detect the virus at very low levels, equivalent to the sensitivity of gold standard PCR tests that can take a day or more to detect. return results from a clinical laboratory.

The technique has several advantages, Wang said. It requires no special preparation or equipment and can be performed at room temperature, so all a user needs to do is mix the sample with the solution and read it. The researchers estimated in their study that the method would cost $1.26 per test.

“Another advantage of this measure is that we can detect the entire virus, which is still infectious, and distinguish it from fragments that may no longer be infectious,” Wang said. Not only will this give patients and doctors a better understanding of whether they are contagious, but it could also significantly improve community-level modeling and tracking of active outbreaks, such as via wastewater.

In addition, the DNA nets inhibited the spread of the virus in live cell cultures, with the antiviral activity increasing with the size of the DNA net scaffold. This points to the potential of DNA structures as therapeutic agents, Wang said.

“I had this idea at the very beginning of the pandemic to build a platform for testing, but at the same time for inhibition,” Wang said. “Many other groups working on inhibitors try to wrap the whole virus, or the parts of the virus that give access to antibodies. That’s not good, because you want the body to start forming antibodies. With the hollow DNA net structures , antibodies still have access to the virus.”

The DNA net platform can be adapted to other viruses, Wang said, and even multiplexed so that a single test can detect multiple viruses.

“We are trying to develop a unified technology that can be used as a plug-and-play platform. We want to take advantage of the high binding affinity, low limit of detection, low cost and rapid preparation of DNA sensors,” Wang said.

The National Institutes of Health supported this work through the Rapid Acceleration of Diagnostics program. The researchers will continue to explore and accelerate clinical applications for the DNA net platform through the RADx program.

Wang is also affiliated with the Holonyak Micro and Nanotechnology Lab and the Carl R. Woese Institute for Genomic Biology in Illinois.

Source:

University of Illinois at Urbana-Champaign

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