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COVID-19: Mutation in spike protein makes virus up to 8 times more infectious

Researchers at New York University, New York Genome Center and Mount Sinai focused on the ‘G variant’ or D614G mutation in the SARS-CoV-2 spike protein that appeared in early 2020 and today the dominant form of the SARS-CoV-2 virus in the United States. “In the months which followed the completion of this study, the prevalence of the D614G mutation has become almost universal since it is present in all the current worrisome variants”, notes the principal author, Neville Sanjana, professor of biology , Neuroscience and Physiology at NYU Grossman School of Medicine.

The mutation that leads to more transmissibility explains the rapid spread of the virus

In this study, the researchers introduced a virus carrying the D614G mutation into cells of the human lung, liver and colon. They also introduced the “wild-type” version of the coronavirus – the version of the virus from the start of the pandemic, free of this mutation – into these same cell types for comparison. The team finds that

  • the D614G variant increases the transmissibility of the virus up to 8-fold compared to the original virus;
  • the virus becomes more resistant to cleavage or division by other proteins: this mechanism may help explain the increased capacity of the variant to infect cells, because the resistance of the variant allows a greater proportion of spike protein to be kept intact by virus;
  • in synthesis, the D614G variant infects human cells much more efficiently than the “wild” strain.

A growing consensus among scientists: a growing number of research teams share this conclusion of greater infectivity of the D614G variant of the spike protein. The authors cite here a number of studies leading to this same conclusion. However, it is not yet clear whether the variant is more virulent, either linked to more severe disease or to an increased risk of hospitalization or death.

Implications for future vaccines: In the spirit of this recent article published in The Lancet, the team suggests that it may be beneficial for future boosters to include different forms of spike protein of different circulating variants. Because the vaccines approved today, as well as those under development, were and are being developed using the original peak sequence.

Finally, this new experimental setup will also make it possible to quickly and specifically assess the contribution of other mutations to the spread of SARS-CoV-2, explains one of the researchers, Tristan Jordan, postdoctoral researcher at Mount Sinai.

“Our research is essential to understand the changes in biology that a viral variant can induce. We are currently clarifying the implications of the different variants that have emerged in the UK, Brazil and South Africa ”.

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