[ad_1]
We know that the coronavirus behind the COVID-19 crisis lived harmlessly to bats and other wildlife before it jumped over the species barrier and spread to humans.
Now, Duke University researchers have identified a series of “silent” mutations in the roughly 30,000 letters of the virus’ genetic code that helped it thrive once it made the leap, and possibly helped set the stage for the pandemic. global. The subtle changes involved how the virus folded its RNA molecules inside 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 humans.
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 positive selection fingerprints within a gene that encodes the “spike” proteins that dot the surface of the coronavirus, which play a key role in its ability to infect new cells.
The new study also pointed to mutations that disrupted 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, called Nsp4 and Nsp16, appear to have given the virus a biological advantage over earlier strains without altering the proteins they encode.
Rather than affecting proteins, Berrio said, the changes likely affected the way the virus’ genetic material, which is made of RNA, folds into three-dimensional shapes and functions within human cells.
What these changes to the RNA structure might have done to differentiate the SARS-CoV-2 virus in humans from other coronaviruses is still unknown, Berrio said. But they may have contributed to the virus’s ability to spread before people know they have it, a crucial difference that made the current situation much more difficult to control than the 2003 SARS coronavirus outbreak.
The research could lead to new molecular targets to treat or prevent 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 is not expressed until later. Therefore, they could be a better therapeutic target because they appear earlier in the viral life cycle. “
More generally, by identifying the genetic changes that allowed the new coronavirus to thrive in human hosts, scientists hope to better predict future outbreaks of zoonotic diseases before they occur.
“Viruses are constantly mutating and evolving,” Berrio said. “Therefore, it is possible that a new strain of coronavirus capable of infecting other animals appears that also has the potential to spread to people, as SARS-CoV-2 did. We will have to be able to recognize it and make efforts to contain it early. “
Citation: Berrio A, Gartner V, Wray GA. 2020. Positive selection within the genomes of SARS-CoV-2 and other coronaviruses regardless of impact on protein function. PeerJ. 2020. 8: e10234 https://doi.org/10.7717/peerj.10234
This article has been republished from the following materials. Note: the material may have been edited for its length and content. For more information, contact the cited source.
[ad_2]
