A press release suggests functional activity for the SARS-CoV-2 substitution D614G

Today several news outlets highlighted a new report suggesting a single amino acid change in the spike protein of SARS-CoV-2 that could alter viral infectivity. This substitution changes the amino acid at position 614 of the viral spike protein from an aspartic acid (D) to a glycine (G). 

SARS-CoV-2 replication in tissue culture cells. The new virus particles are highlighted in blue.

The D614G virus, as it is identified, is predominantly on the East Coast of the United States, and the D strain is predominantly on the West Coast. It was first identified in a bioinformatics report a month ago where it was proposed that because of dominance of this strain in several areas of the world the amino acid change had improved the virus’ infectivity and ability to survive in humans.

At that time the report on D614G was criticized because there was no biological data supporting a functional change in the virus. Yesterday, researchers at Scripps Research, Florida, announced that the D614G substitution stabilized the virus’s spike proteins and increases the number of these proteins on the surface of the virus. The number of functional and intact spikes on each viral particle was about five times higher because of this mutation, they found. 

The investigators also reported that this substitution increased viral infection and growth in tissue culture. They attributed this to increased numbers of viral spike proteins, which bind to host cell ACE2 proteins, a crucial step in viral infection in cells. While the paper has yet to be peer reviewed the Scripps Florida Institute, where the investigators work, put out a press release on the finding.

It is impossible to evaluate the science involved in these studies, since the paper is not published or peer-reviewed. Despite this, it come from a reputable institution and group. These are scientists who can easily do the studies that were described in the press release and show a difference in the replication rate and infectivity of the virus in tissue culture. 

However, even if the D614G change allows the virus to grow more efficiently in tissue culture this does not mean that the virus will show differences in infectivity in either animals or humans. An example of this was shown with Ebola virus, where nucleotide changes improved virus replication in tissue culture, but did not alter infectivity in either animals or humans.

Thus, the press release is very provocative and may suggest that even a single amino acid change in SARS-CoV-2 can lead to increased infectivity. However, I would very much hold judgment on this until the paper can be reviewed and the studies are shown to have significance in humans.

One comment on this came from Dr. Kristian Andersen, a geneticist at Scripps Research, La Jolla, California. She said that analyses of D614G and other variants in Washington and California had so far found no difference in how quickly or widely one variant spread over another.

“That’s the main reason that I’m so hesitant at the moment,” Andersen said. “Because if one really was able to spread significantly better than the other, then we would expect to see a difference here, and we don’t.”

If there is significance to this work, it may be that this particular structural change may be a target for drug therapy. Also see this site https://d614g.com

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

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