New virus-like probes may increase the reliability of the COVID-19 test

Researchers have developed two new virus-like probes called positive controls to validate the COVID-19 test. The team suggests that the controls are more stable, easier to manufacture, and cheaper than the controls currently used for COVID-19 testing.

Positive controls are used to validate tests and experiments and are an important part of the lab toolkit. However, scientists have suggested that there may be a problem with the controls currently used to validate the COVID-19 test. According to nanoengineers at the University of California, San Diego (UC San Diego), most probes used to validate rapid COVID-19 tests are naked synthetic RNA, plasmids, or RNA samples from infected patients and are easily degraded. , Needs refrigeration to maintain activity. .. Scientists said this was inconvenient and costly to ship worldwide and to store for extended periods of time.

In a new study published in ACS nanoResearchers at the University of California, San Diego, Jacobs Institute of Technology have sought to design positive controls that are more stable, easier to manufacture, and cheaper. This article details the development and testing of two different controls made from virus-like particles that express a segment of RNA from the SARS-CoV-2 virus (which causes COVID-19).

“Our goal is to impact not only hospitals with state-of-the-art facilities, but also resource-poor and under-served areas that may lack advanced infrastructure and trained personnel. “Nicole Steinmetz said. Research leader and professor of nanoengineering at the University of California, San Diego, Jacobs Institute of Technology.

The team has developed two different controls. One was made from plant virus nanoparticles and the other was made from bacteriophage nanoparticles. According to scientists, both can be stored at temperatures up to 40 ° C for a week and maintain 70% of their activity after a month of storage. It can also pass detection as SARS-CoV-2 coronavirus without infection.

Plant virus-based controls use cowpea chlorotic mottle virus, which infects cowpea plants. To develop the probe, researchers opened the virus, removed its RNA contents, replaced it with a synthetic RNA template containing a specific sequence of SARS-CoV-2 virus, and then closed the virus shell.

To create a bacteriophage-based control, researchers inserted the gene sequence of interest from the SARS-CoV-2 virus and the gene encoding the surface protein of bacteriophage Qbeta into the plasmid. When these plasmids are introduced into the bacterium, they reprogram them to produce virus-like particles with the SARS-CoV-2 RNA sequence on the inside and the Qbeta bacteriophage protein on the outside.

Both controls were validated in clinical samples.

According to researchers, one of the advantages of their probe is that it can be used in all steps of the COVID-19 test in parallel with the patient’s sample, unlike the COVID-19 test controls currently in use. The team says this will make it easier to identify if a problem occurred early in the analysis.

So far, researchers have adapted their controls for use in RT-PCR tests approved by the US Centers for Disease Control and Prevention (CDC). This is currently the gold standard for the COVID-19 test, but the team states that it is expensive, complex and can take days to return results due to the need for specialized lab equipment.

Nanoengineers are now adapting controls for use in less complex COVID-19 diagnostic tests, such as the RT-LAMP test, which can be run out-of-lab and provide immediate results.

Steinmetz concludes: “Making low-tech assays more accurate is a relatively simple nanotechnology approach that helps break down some barriers to population testing of underserved populations in the United States and around the world. There is a possibility.”