How we could turn COVID against itself

For the last 18 months we have been washing our hands, wearing masks and vaccinating to fight the coronavirus. But could we make the virus do battle with itself and fight COVID with COVID?

Researchers at Penn State University have designed a proof-of-concept treatment that might be able to do just that.

Viruses thrive because they invade the cells of other organisms, forcing them to create viral proteins and genetic material so the virus can replicate, before bursting out of the cell to start the whole process again.

The team at Penn State designed a synthetic version of the SARS-CoV-2 virus that interferes with the real virus’s growth. They say that it could potentially wipe out both the ‘real’ virus and the synthetic version.

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“In our experiments, we show that the wild-type [disease-causing] SARS-CoV-2 virus actually enables the replication and spread of our synthetic virus, thereby effectively promoting its own decline,” said Marco Archetti, associate professor of biology, Penn State. “A version of this synthetic construct could be used as a self-promoting antiviral therapy for COVID-19.”

According to Archetti, these ‘defective interfering’ (DI) viruses are common in nature, and contain large deletions in their protein-coding genes that hinder their ability to replicate themselves. However, if they manage to infect a cell that also contains a ‘wild-type’ virus, they can hijack its machinery and replicate themselves. When a DI virus uses wild-type virus machinery, it can also impair the growth of the wild-type virus. Thanks to their shorter genome, these DI viruses could even replicate faster, out-competing the wild-type virus.

“These defective genomes are like parasites of the wild-type virus,” said Archetti.

To carry out the study, the team took a SARS-CoV-2 genome and used it to engineer synthetic DI genomes. They then introduced these DI genomes to monkey cells that had been infected with wild-type SARS-CoV-2.

After 24 hours, they found that the DI genome replicated three times faster than wild-type SARS-CoV-2, and viral load was reduced by half.

Archetti says that while a reduction of half in 24 hours is not enough for therapeutic purposes, further experiments need to be carried out. In unpublished research, the scientists have tried using nanoparticles as a delivery vector, and saw the virus decline by more than 95 per cent in 12 hours.

“With some additional research and fine-tuning, a version of this synthetic DI could be used as a self-sustaining therapeutic for COVID-19,” said Archetti.

Read more about the coronavirus:

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"This is an interesting proposal as defective interfering viruses can indeed inhibit the replication of the regular pathogenic version of the virus,” said Dr Jeremy Rossman, a virologist who was not involved in the research. “However, it is unlikely this would ever be a viable way to stop the spread of COVID-19.

"First, we don’t know if in fact a defective interfering SARS-CoV-2 virus would prevent all human clinical disease, including long COVID.

"Second, the use of any live virus as a vaccine or therapeutic has to ensure that continued virus evolution does not risk the defective virus causing disease or changing how the regular pathogenic version of the virus behaves.

"Third, for the defective interfering virus to inhibit the normal version of the virus, the same person has to be simultaneously infected with both versions of the virus. Infection with the defective version would not persist in a person until they got subsequently infected and so it is unlikely this would ever be a viable way to stop COVID, though it is an intriguing concept.”