Just a year after winning the Nobel Prize in Chemistry, Jennifer Doudna has achieved a new breakthrough for science and humanity.
The experienced biochemist and her colleagues at the University of California at Berkeley and the Gladstone Institute of Virology (San Francisco) identified in the Delta variant of the coronavirus a mutation that allows it to spread in the body very quickly, a characteristic that could be linked to its greater contagion capacity, according to the new study published in Science.
So far, it is known that Delta has an advantage over other SARS-CoV-2 variants due to mutations (genetic changes) that enhance its protein S, the part of the virus that allows it to enter the human cell.
However, there are mutations that have not been studied because their effects occur inside the virus. There is the nucleocapsid, also called protein N, which is responsible for storing genetic material (RNA) and releasing it within the cell to replicate and produce thousands of viral copies.
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A novel technique
To unravel this mystery, Doudna’s team developed virus-mimicking particles with all parts of SARS-CoV-2 and modified their N protein with mutations present in known variants.
When they infected the cells with these particles, they observed that those with the R203M mutation, also present in the N protein of the Delta variant, produced 10 times more RNA copies compared to the original virus.
This result was, in Doudna’s words, “a surprise.” But they still had to corroborate them. So they moved to a laboratory with high-level biosafety conditions: it was time to test with real viruses.
Scientists inserted the R203M mutation into a coronavirus. When it entered lung cells, it produced 51 times more infectious virus than the original strain of SARS-CoV-2.
In people infected with coronavirus, a very small percentage of viral particles produced by one cell are capable of infecting other cells. One reason for this is that they lack RNA fragments or all of this genetic material, explains Science magazine.
But it seems that the R203M mutation makes the virus more efficient at placing RNA in the new viral copies.
“This mutation found in Delta makes the virus better at producing infectious particles and therefore spreads faster”said biomedical engineer Abdullah Syed, a co-author of the study.
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Objective of future treatments
Research reveals that this mutated part of the N protein is a powerful weapon that the Delta variant takes advantage of during infection. However, it also poses an opportunity to counter this contagious version of the coronavirus.
“Scientists in this area of research might think more about targeting the nucleocapsid protein (N) to actually help control infection and to treat patients, ”said Shan Lu, a cell biologist at the University of California, San Deigo and a researcher of protein N.
A first step will be to understand how R203M and other mutations in the N protein enhance the production of infectious viral particles.
If they discover that a protein in the cell is involved in this process, they could design a drug to ‘deactivate’ it and thus stop the spread of Delta in the body of those infected. And the less viruses, the less likely that the infections will continue.
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Nobel Prize winner in Chemistry discovers the ‘hidden weapon’ of the Delta variant