“RNA Folding” And “Silent Mutations” May Help COVID-19 Virus to Evolve

Mechanism of “RNA folding” and the underlying role of “silent mutations” in its process may help explaining why coronavirus is evolving rapidly despite all the efforts to control the virus.

It has become challenging to understand the zoonotic events by identifying the genetic changes that allow a pathogen to infect a new host is critical. It can help in better understanding of underlying processes in both the pathogen and the host. It is lucid based on a study that SARS-CoV-2 Covid-19 virus exists in as benign harmless form in bats and other wildlife populations before it is transferred to humans where it is considered harmful.

The study published in the Bioinformatics and Genome , implicates that the existing silent mutations can help in understanding the underlying factors that predispose to the virulence of the virus. A group of Duke researchers in the study have unrevealed a set of silent mutations among the 30,000 base pairs of the virus’s genetic code that allowed the virus to populate via replication with efficiency while it jumped to humans.

Further they explained how these silent mutations help the virus to undergo structural changes to “fold” its RNA molecules inside human cells.

“RNA folding” is a complex process where the genetic content RNA goes through structural states from the unfolded disordered state to its ideal working or functional form of the folded state. The RNA folding mechanism is critical to better elucidate its specific functions in cells as it must fold into specific 3-D structures to confer the virulence.

As RNA has one thread like strand that can fold back on itself by forming glue like base pairs, resulting better functional capacity relative to DNA. However, it is difficult at the same time to “engineer” RNA into the human cell due to greater complexity. Yet, the SARS-CoV-2, Covid-19 virus efficiently enters the RNA into human cell.

Since the virus outbreak, efforts have been prompted to understand the genetic basis for its unique characteristics and its efficacy to jump to humans. In the study, researchers tested the mutations and unrevealed a set of silent mutations among the 30,000 base pairs of the virus’s genetic code that allowed the virus to populate via replication with efficiency while it jumped to humans.

Source: BMC

It was found that the gene encoding spike protein is considered the founding factor in causing virulence. Researchers also determined the mutations that altered the spike protein structure that implies different viral strains of SARS-CoV-2 carry these mutations are more likely to populate. Furthermore, two novel mutations were identified that have yet to be identified.

The lead author Alejandro Berrio, Wray lab, Department of Biology, Duke University, while talking to a press release, said, “We’re trying to figure out what made this virus so unique.”

“Nsp4 and Nsp16 are among the first RNA molecules that are produced when the virus infects a new person,” Berrio added.

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