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'Silent" Mutations Gave COVID-19 Evolutionary Edge

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RNA folding may help explain how the coronavirus became so hard to stop after it spilled over from wildlife to humans.

SARS-CoV-2, the coronavirus that causes COVID-19, appears to have evolved silent changes to its RNA code that gave it a biological edge over previous strains.

Credit: Felipe Esquivel Reed

We know that the coronavirus behind the COVID-19 crisis lived harmlessly in bats and other wildlife before it jumped the species barrier and spilled over to humans.

Now, researchers at Duke University have identified a number of “silent” mutations in the roughly 30,000 letters of the virus’s genetic code that helped it thrive once it made the leap — and possibly helped set the stage for the global pandemic. The subtle changes involved how the virus folded its RNA molecules within human cells.

For the study, published Oct. 16 in the journal PeerJ, the researchers used statistical methods they developed to identify adaptive changes that arose in the SARS-CoV-2 genome in humans, but not in closely related coronaviruses found in bats and pangolins.

“We’re trying to figure out what made this virus so unique,” said lead author Alejandro Berrio, a postdoctoral associate in biologist Greg Wray’s lab at Duke.

Previous research detected fingerprints of positive selection within a gene that encodes the “spike” proteins studding the coronavirus’s surface, which play a key role in its ability to infect new cells.

The new study likewise flagged mutations that altered the spike proteins, suggesting that viral strains carrying these mutations were more likely to thrive. But with their approach, study authors Berrio, Wray and Duke Ph.D. student Valerie Gartner also identified additional culprits that previous studies failed to detect.

The researchers report that so-called silent mutations in two other regions of the SARS-CoV-2 genome, dubbed Nsp4 and Nsp16, appear to have given the virus a biological edge over previous strains without altering the proteins they encode.

Instead of affecting proteins, Berrio said, the changes likely affected how the virus’s genetic material — which is made of RNA — folds up into 3-D shapes and functions inside human cells.

What these changes in RNA structure might have done to set the SARS-CoV-2 virus in humans apart from other coronaviruses is still unknown, Berrio said. But they may have contributed to the virus’s ability to spread before people even know they have it — a crucial difference that made the current situation so much more difficult to control than the SARS coronavirus outbreak of 2003.

The research could lead to new molecular targets for treating or preventing COVID-19, Berrio said.

“Nsp4 and Nsp16 are among the first RNA molecules that are produced when the virus infects a new person,” Berrio said. “The spike protein doesn’t get expressed until later. So they could make a better therapeutic target because they appear earlier in the viral life cycle.”

More generally, by pinpointing the genetic changes that enabled the new coronavirus to thrive in human hosts, scientists hope to better predict future zoonotic disease outbreaks before they happen.

“Viruses are constantly mutating and evolving,” Berrio said. “So it’s possible that a new strain of coronavirus capable of infecting other animals may come along that also has the potential to spread to people, like SARS-CoV-2 did. We’ll need to be able to recognize it and make efforts to contain it early.”

CITATION: “Positive Selection Within the Genomes of SARS-CoV-2 and Other Coronaviruses Independent of Impact on Protein Function,” Alejandro Berrio, Valerie Gartner, Gregory A Wray. PeerJ, October 16, 2020. DOI: 10.7717/peerj.10234

Contacts and sources:
Robin A. Smith 
Duke University

Publication: Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function.
Alejandro Berrio, Valerie Gartner, Gregory A. Wray. PeerJ, 2020; 8: e10234 DOI: 10.7717/peerj.10234

 



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    Total 6 comments
    • Jamais Vu

      Were they “silent” because they were engineered in a quiet Chinese lab?

    • Fake News = The False Prophet

      “First, in the section titled ‘Whole Genome Sequencing,’ we find that rather than having isolated the virus and sequencing the genome from end to end, they found 37 base pairs from unpurified samples using PCR probes. This means they actually looked at 37 out of the approximately 30,000 of the base pairs that are claimed to be the genome of the intact virus. They then took these 37 segments and put them into a computer program, which filled in the rest of the base pairs.”

      “’Therefore, we examined the capacity of SARS-CoV-2 to infect and replicate in several common primate and human cell lines, including human adenocarcinoma cells (A549), human liver cells (HUH 7.0), and human embryonic kidney cells (HEK-293T). In addition to Vero E6 and Vero CCL81 cells [monkey cells]. … Each cell line was inoculated at high multiplicity of infection and examined 24h post-infection. No CPE was observed in any of the cell lines except in Vero [monkey] cells, which grew to greater than 10 to the 7th power at 24 h post-infection. In contrast, HUH 7.0 and 293T showed only modest viral replication, and A549 cells [human cells] were incompatible with SARS CoV-2 infection’.”

      “The shocking thing about the above [CDC journal] quote is that using their own methods, the virologists found that solutions containing SARS-CoV-2 — even in high amounts — were NOT, I repeat NOT, infective to any of the three human tissue cultures they tested. In plain English, this means they…

      • Fake News = The False Prophet

        In plain English, this means they proved, on their terms, that this ‘new coronavirus’ is not infectious to human beings. It is ONLY infective to monkey kidney cells, and only then when you add two potent drugs (gentamicin and amphotericin), known to be toxic to kidneys, to the mix.”

        “My friends, read this again and again. These virologists, published by the CDC, performed a clear proof, on their terms, showing that the SARS-CoV- 2 virus is harmless to human beings. That is the only possible conclusion, but, unfortunately, this result is not even mentioned in their conclusion. They simply say they can provide virus stocks cultured only on monkey Vero cells, thanks for coming.”

    • Fake News = The False Prophet

      In other words there is no COVID19. They have made it ALL up. No Wuhan, No Trump has it, Nobody has died from it. Contagion has never been proven. Isolated samples do not exist. Further if this is an indication of how these clowns perform ‘science’ then it’s more than likely that NO VIRUS has ever been isolated or proven to cause contagion.

      Whoever has died has not died of this so called pandemic. It doesn’t exist except in the minds of lunatics.

      VIRUS is a very interesting coded word.

      • Jamais Vu

        There are no anagrams for the word “virus”. But, I’ll assume you’ll tell us what the coded meaning is?

        • CUB4DK

          …possibly a code based on someone’s consciousness :?:

          Feels like a Hollywood Sci-Fi episode for some funny reason…Hmmmm

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