Fighting COVID With COVID: Driving the Disease to Extinction With a Defective Version of the SARS-CoV-2 Virus

Coronavirus SARS-CoV-2 Virus Illustration

Researchers design new COVID-19 therapy that uses a defective version of the SARS-CoV-2 virus to drive the disease-causing version to extinction.

What if the COVID-19 virus could be used against itself? Researchers at Penn State have designed a proof-of-concept therapeutic that may be able to do just that. The team designed a synthetic defective SARS-CoV-2 virus that is innocuous but interferes with the real virus’ growth, potentially causing the extinction of both the disease-causing virus and the synthetic virus.

“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.”

Archetti explained that when a virus attacks a cell, it attaches to the cell’s surface and injects its genetic material into the cell. The cell is then tricked into replicating the virus’ genetic material and packaging it into virions, which burst from the cell and go off to infect other cells.

“Defective interfering” (DI) viruses, which are common in nature, contain large deletions in their genomes that often affect their ability to replicate their genetic material and package it into virions. However, DI genomes can perform these functions if the cell they’ve infected also harbors genetic material from a wild-type virus. In this case, a DI genome can hijack a wild-type genome’s replication and packaging machinery.

“These defective genomes are like parasites of the wild-type virus,” said Archetti, explaining that when a DI genome utilizes a wild-type genome’s machinery, it also can impair the wild-type genome growth.

In addition, he said, “given the shorter length of their genomes as a result of the deletions, DI genomes can replicate faster than wild-type genomes in coinfected cells and quickly outcompete the wild-type.”

Indeed, in their new study, published in the journal PeerJ, Archetti and his colleagues found that their synthetic DI genome can replicate three times faster than the wild-type genome, resulting in a reduction of the wild-type viral load by half in 24 hours.

To conduct their study, the researchers engineered short synthetic DI genomes from parts of the wild-type SARS-CoV-2 genome and introduced them into African green monkey cells that were already infected with the wild-type SARS-CoV-2 virus. Next, they quantified the relative amounts of the DI and WT genomes in the cells over time points, which gave an indication of the amount of interference of the DI genome with the wild-type genome.

The team found that within 24 hours of infection, the DI genome reduced the amount of SARS-CoV-2 by approximately half compared to the amount of wild-type virus in control experiments. They also found that the DI genome increases in quantity 3.3 times as fast as the wild-type virus.

Archetti said that while the 50% reduction in virus load that they observed over 24 hours is not enough for therapeutic purposes, presumably, as the DI genomes increase in frequency in the cell, the decline in the amount of wild-type virus would lead to the demise of both the virus and the DI genome, as the DI genome cannot persist once it has driven the wild-type virus to extinction.

He added that further experiments are needed to verify the potential of SARS-CoV-2 DIs as an antiviral treatment, suggesting that the experiments could be repeated in human lung cell lines, and against some of the newer variants of SARS-CoV-2. Furthermore, he said, an efficient delivery method should be devised. In further work that is still unpublished, the team has now used nanoparticles as a delivery vector and observed that the virus declines by more than 95% 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.

Reference: “A synthetic defective interfering SARS-CoV-2” by Shun Yao, Anoop Narayanan, Sydney A. Majowicz, Joyce Jose​ Marco Archetti​, 1 July 2021, PeerJ.
DOI: 10.7717/peerj.11686

Other Penn State authors on the paper include Shun Yao, postdoctoral scholar in biology; Anoop Narayanan, associate research professor of biochemistry and molecular biology; Sydney Majowicz, graduate student in molecular, cellular and integrative biosciences; and Joyce Jose, assistant professor of biochemistry and molecular biology.

The Huck Institutes of the Life Sciences at Penn State supported this research.

6 Comments on "Fighting COVID With COVID: Driving the Disease to Extinction With a Defective Version of the SARS-CoV-2 Virus"

  1. Sci-tech and Sci-fi cross: Will Smith? Alice Braga? “I Am Legend”? The Krippen Virus? I hear you:”I know what let’s do! Let’s TRICK with something REALLY dangerous!” All in the name of commercially driven, “SCIENTIFIC” one-up-personship. Are you trippin’? Better make sure those dudes and dudettes at the Lab don’t fatigue-out some night, accidentally REVERSE the bio-filter flow and flush that Puppy into the Common Atmosphere. CAN’T HAPPEN HERE!? It can and it did, once-upon-a-time in Denver… Hmm… wasn’t that a movie or sumthin’… from the 80s? Yeah. Theatre of the REAL.

    • Exactly, Alexiev, as you said, “Theatre of the REAL.”

      A perceptive 10 year old can see, and could see from the start, that Covid-19 has nothing to do with real science (ie, it’s a holocaustal scam).

      Here is WHY even most so-called intelligent people CANNOT figure that out… read “The 2 Married Pink Elephants In The Historical Room –The  Holocaustal Covid-19 Coronavirus Madness: A Sociological Perspective  & Historical Assessment Of The Covid “Phenomenon”” by Rolf Hefti at 

  2. I consider theatre of the real being more like 10% of the human population having a CCR5 mutation that makes them somewhat or fully immune to HIV, or maybe a virus getting whatever the viral form of Huntington’s is and being crippled. But unfortunately the real has less capitalized words outside of acronyms and liberal use of exclamation points.

  3. Howard Jeffrey Bender, Ph.D. | August 20, 2021 at 12:57 pm | Reply

    It’s a bit unclear to me how the defective virus can “hijack” the real virus machinery, which is only its mRNA. Certainly the defective virus can put in its own defective mRNA, but that’s overloading, not hijacking. Here’s another idea.

    All the variants have different protein spikes, with Delta having one that’s more efficient at getting around the vaccines. But the real problem is in the virus and why the most dangerous, MERS, SARS, and Covid-19, are so infectious. My independent research has found multiple one-in-a-million nucleotide sequence matches between all the coronaviruses and the human genome. Those sequences are the same as some of the loops of human tRNA. Using those loops and their amino acid code matches, viruses may be able to fool the nucleus membrane in cells to allow the virus to enter and associate with the human DNA, creating more opportunities for further infection. Our immune system may be compromised and may no longer be able to stop the virus and other diseases from attacking organs throughout the body. Vaccines that attack the virus protein shells while ignoring their contents are doomed to failure from the Darwin effect, but recognizing these loops suggests a possible approach to successful coronavirus vaccines. Only the infection process is considered in my work, not the innate virulence of the virus. For more info, check out this YouTube, Coronavirus – Using Your DNA Against You.

  4. Sounds just as insane as mutating a virus on purpose in ferrets, building a nuclear rector that goes critical if it looses power, or having scentists be paid by corperations to produce the very reports that their products need to be profitable.

  5. I wonder if this will cause people to grow a third eye like what’s going to happen in a few years from covid vaccines. /s

    Amazing.. sounds similar to sending out sterile mosquitos.

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