The D614G variant of SARS CoV-2 coronavirus is in the news again.

This coronavirus variant first gained attention in May because of a bioinformatics manuscript that suggested the substitution of this single amino acid in a viral protein [Spike (S) protein] had created a dominant virus that had become the primary type of coronavirus identified in Europe and the east coast of the United States. That paper was not peer reviewed but published on Biorxiv.org, a preprint website.

Coronavirus with several of its membrane proteins. The Spike (S) protein binds to the cell ACE2 protein.

Online reviews quickly pointed out a number of problems with that manuscript, especially the fact that there was no biology or evidence to support the claim that this virus was more infectious or dominant over versions that do not have the single amino acid substitution. It was dismissed and has yet to be formally published.

The spike protein binds to the ACE protein on the target cell and facilitates coronavirus entry.
Dr. Hyeryun Choe

A recent study from the Scripps Institute in Florida by Dr. Hyeryun Choe suggested that the virus with this single immunity amino acid substitution had more stabilized and higher levels of the Spike binding protein for the ACE2 target protein. This paper suggested that because of this the virus might be more infectious. 

The spoke protein is made from hundreds of amino acids!

Today, another manuscript in Biorxiv.org from Professor Huang Ailong at Chongqing Medical University, suggested that antibodies found in patients who had been infected with earlier forms of SARS-CoV-2 failed to neutralize the D614G substituted strain. This paper was highlighted by the South China Morning news and several other news services including STAT. It raised significant concern that individuals infected with other forms of SARS-CoV-2 might be susceptible to reinfection with the D614G version. 

First, all of these manuscripts have been made available without peer review on the Biorxiv.org, a preprint website. Importantly, all have crucial technical flaws in their studies. I will highlight the central issues with the last two manuscripts.

The Scripps group used a pseudo-virus, a synthetic retrovirus with the spike protein (not real COVID-19) to look at viral binding to target cells.  They observed that the pseudo-viruses (retroviruses with the SG614 substitution) infected ACE2 expressing cells more efficiently than those with the parent amino acid. They believe this was the result of more of the S protein on the virus as it was correlated with less spike protein shedding and greater incorporation of the S protein into the pseudo virus. 

Confounding that hypothesis, however, G614 did not bind ACE2 more efficiently than D614. Importantly, the pseudo-viruses containing these Spike proteins were neutralized with comparable efficiencies by convalescent plasma from patients infected with “regular” COVID-19. This suggested that immunity was not evaded by this substitution. Despite this, they claimed that the “results show Spike G614 is more stable than Spike D614, consistent with epidemiological data suggesting that viruses with Spike G614 transmit more efficiently.” This is a true leap of faith since they did not identify a mechanism for the increased infectivity.

The Chongqing Medical University study was even less persuasive. Again, it used artificial viruses to examine the ability to “neutralize” the D614G version of SARS-CoV-2. Importantly, even in this system 93% (38/41) sera from convalescent COVID-19 patients could neutralize both original and D614G substituted pseudo-viruses with comparable efficiencies, while only 7% (3/41) convalescent sera showed decreased neutralizing activity against S-G614 pseudo-virus.

Aside from the fact that the artificial viruses used in these studies do NOT accurately represent natural infection in COVID-19, there are bigger problems with the concept that this change allows the virus to escape immune control. These proteins are made up of hundreds of amino acids, and changing just one does not alter most of the immune recognition sites.

I can assure you that overall immunity cannot be circumvented by a single amino acid substitution in an entire virus. Both of these studies actually showed that immune protection was maintained against D614G.

I ask the media, please stop publishing these headlines without science to back them up!

Published by jbakerjrblog

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

4 thoughts on “The D614G variant of SARS CoV-2 coronavirus is in the news again.

  1. Let me begin by saying I love your blog. However, I have become put off lately by the lack of good proofreading, which results in many misspellings or misplaced and omitted words. Sometimes I can’t figure out what you meant to say. In your blog today, the word “spoke” appeared in place of “spike” in the caption under a chart! Unfortunately, sloppiness like this can make your readers question the validity of your work and the information contained in your blog. Please be more careful.. Perhaps someone more competent than Biscuit needs to take over as proofreader!

    Like

  2. I am a grammar fiend too, but I appreciate the common sense positions you put forth, with hard core science to back them up. When you give glimmers of hope, I know I can believe you. And Biscuit can help you any way he pleases. Thank you so much.

    Liked by 1 person

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