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Coronavirus COVID-19. 3d render
It is clear that SARS-CoV-2, the virus responsible for Covid-19, existed benignly in bats and other wildlife populations before it reached humans.
But the stability of the virus in bats and other wildlife populations, the result of so-called “silent mutations,” can also potentially help explain its virulence, setting the stage for the current global pandemic.
The Duke researchers have now discovered a set of these silent mutations among the 30,000 base pairs of the virus’ genetic code that allowed it to replicate as efficiently as it would jump humans. Ultimately, these mutations imply how the virus has managed to “fold” its RNA molecules within human cells.
“RNA folding” is the intricate process of how RNA transitions from an unfolded disorderly state to its ideal working or functional form, that is, the folded state. RNA folding is important because in order to perform its specific functions in cells, it must fold into specific three-dimensional structures. Because a single strand of RNA can fold back on itself to form base pairs, it results in greater functional capacity compared to DNA. However, at the same time, “engineering” also becomes more challenging due to increased complexity.
For the study, the researchers relied on a statistical algorithm they developed to identify adaptive mutations that developed in the SARS-CoV-2 genome in humans, but were not seen in closely related coronaviruses found in bats and pangolins. .
“We are trying to find out what made this virus so unique,” said lead author Alejandro Berrio in a Press release.
Previous research has detected so-called positive selection (Darwinian) “fingerprints” within a gene encoding the “spike” proteins that cover the surface of the coronavirus, which is now known to play a key role in the ability of SARS- CoV-2 to infect new cells. The spike protein allows the virus to adhere to and infect the host cell by binding to angiotensin-converting enzyme receptor 2 (ACE2).
The new study also identified mutations that disrupted spike proteins, implying that viral strains carrying these mutations were also more likely to thrive. But the researchers also highlighted two new candidates for mutations that have yet to be identified, as the genetic sequence of SARS-CoV-2 was shared publicly for the first time. (January 12, 2020)
The researchers found that silent mutations in two other regions of the SARS-CoV-2 genome:Nsp4 and Nsp16—It seems to have given the virus a biological advantage over previous strains, but without changing the structure of the proteins they encode.
Rather than influencing the proteins themselves, these mutations likely affected the way that SARS-CoV-2 genetic material, made up of RNA, folds into different three-dimensional shapes and functions within human cells.
The researchers believe that mutations in the RNA folding may have allowed the virus to spread rapidly and asymptomatically before detection, in contrast to the SARS outbreak during 2002-2003. The authors also suggest that the results of their research may also lead to new molecular targets for treating or preventing COVID-19.
“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.”
The implication is also that by identifying specific genetic changes that allowed SARS-CoV-2 to survive and reproduce in human hosts, we will be better equipped to predict and respond to future outbreaks when such viruses jump to humans, potentially before they occur. .
“Viruses are constantly mutating and evolving,” Berrio said. “So it is possible that a new strain of coronavirus capable of infecting other animals will appear that also has the potential to spread to people, as SARS-CoV-2 did. We will need to be able to recognize it and make efforts to contain it early. “.
