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The ‘silent’ mutations that gave the covid evolutionary advantage to be relentless

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For the study, statistical methods were used to identify the adaptive changes that arose in the SARS-CoV-2 genome in humans, but not in bats and pangolins.

Nearly the pandemic year, considering the first cases of coronavirus originating in Wuhan city in early December 2019, there are still many unknowns about SARS-CoV-2. Several studies have confirmed that the virus lived harmlessly in bats and other wildlife before it jumped over the species barrier and spread to humans. Now, Duke University researchers have identified a number of ‘silent’ mutations in the approximately 30,000 letters from the covid-19 genetic code that helped it thrive once it made that leap.

For the study, published in the scientific journal ‘PeerJ’, statistical methods have been used to identify the adaptive changes that arose in the SARS-CoV-2 genome in humans, but not in the coronavirus found in bats and pangolins. Thus, the subtle changes that involve how the virus introduces its RNA molecules into human cells were detected.

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

Previous research has detected a gene that encodes the “spike” proteins that covers the surface of the coronavirus and plays a key role in its ability to infect new cells, but this study also points to mutations that alter spike proteins. This suggests that mutated viral strains have a higher chance of thriving.

The report points out that so-called ‘silent’ mutations in two other regions of the SARS-CoV-2 genome, called Nsp4 and Nsp16, appear to have given the virus a biological advantage over earlier strains without altering the proteins they encode.

Nsp4 and Nsp16 are among the first RNA molecules that are produced when the virus infects a new person

Rather than affecting proteins, according to Berrio, the changes “probably affect the way the virus’s genetic material,” which is made of RNA, “folds into three-dimensional shapes and functions” within human cells.

“Nsp4 and Nsp16 are among the first RNA molecules that are produced when the virus infects a new person,” explains Berrio and continues: “The spike protein is not expressed until later. Therefore, they could be a better therapeutic objective because they appear earlier in the viral life cycle”.

It is still unknown what could have caused these changes in RNA structure to differentiate the SARS-CoV-2 virus in humans from other coronaviruses, but it may have contributed to the virus’s ability to spread before people know it, a crucial difference that has made this pandemic so difficult to control.

More generally, by identifying genetic changes that allowed the new coronavirus to thrive in human guests, scientists hope to better predict future outbreaks of zoonotic diseases before they occur. Although they warn: “Viruses are constantly changing and evolving. A new strain of coronavirus may appear capable of infecting other animals that also have the potential to spread to people, as SARS-CoV-2 did.”

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