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Sep 14, 2022
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COVID-19 mutations accelerated by virus-fighting enzyme

COVID-19 mutations accelerated by virus-fighting enzyme

Researchers have found the first experimental evidence to explain why the COVID-19 virus produces variants like the delta and omicron so quickly. The results of the study, published Sept. 13 in the journal Scientific Reports, could help scientists predict the emergence of new strains of coronavirus and possibly even create vaccines before these strains emerge.

The relatively rapid emergence of numerous variants of the COVID-19 virus has puzzled researchers because most coronaviruses do not mutate or evolve that quickly. This is because they have a built-in “proofreader” mechanism to prevent mutations, as they create copies of themselves as they grow and reproduce in our cells.

But USC scientists have figured out how the COVID-19 virus bypasses the corrector: It hijacks enzymes in human cells that normally protect against viral infections and uses those enzymes to alter its genome and create variants.

According to lead researcher Xiaojiang Chen, professor of biological sciences and chemistry at the Dornsife College of Letters, Arts and Sciences at the University of Southern California, the findings could prove vital to containing the pandemic by helping to prevent new outbreaks of infection caused by new variants.

“New strains can become increasingly infectious and evade the protection of an existing vaccine,” Chen said. “Predicting new options and preparing effective vaccines ahead of time can stop new options before they spread”

Chen and the USC team infected human cells with the coronavirus in the lab and then studied the changes in the virus’ genome as it replicated itself inside the cells.

The sequence of the genetic code of the virus, which consists of DNA, a close relative of RNA, uses four letters to designate the nucleotides of the components: A, C, G, U. During the analysis, Chen and his team noticed an interesting pattern: Many mutations that arose during the replication of the virus, were caused by replacing one specific nucleotide in the code with another – the letter “C” changed to “U”.

The high frequency of C-to-U mutations led them to a group of enzymes that cells often use to protect themselves from viruses. Called APOBEC, these enzymes convert the Cs in the virus genome into Us in order to induce lethal mutations.

However, Chen and his team found that for the COVID-19 virus growing in human cells, C mutations in Us are not only not fatal, but also benefit the virus by allowing it to mutate, evolve and create new strains faster than expected.

“We have provided the first experimental evidence that our own enzymes can help the COVID-19 virus mutate rapidly,” Chen said. “Somehow, the virus has learned to shift the responsibility for its evolution and fitness to the host’s APOBEC enzymes.”

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