The coronavirus is mutating, no cause for alarm...but keep an eye on D614G

[bennevisplace]

This is a good readable summary.

abc.net.au/news/health/2020...

[Fran57]

Hi.

Great article. Thanks for that. Stay safe.

Fran 😉

[bennevisplace in reply to Fran57]

Thanks Fran, you too.

[studebaker]

Interesting article. Silver lining is that, the mutations don’t make them more deadly.

Hopefully, we will have vaccine soon.

Thank you for posting.

Dana

[SeymourB]

The TL;DR is:

We're good. This is an old mutation, and the changes it has wrought are already evident in the increased spread of the virus, but it won't affect vaccines or convalescent plasma.

Articles like this sometimes imply that the information is new and game changing. This is old news. In addition, such articles may cast doubt on vaccines and targeted MAB (monoclonal antibody) drugs. There's no problem with that, either.

I don't expect everyone to nerd out to this level. This is for those of you that are saying, "Hey! What? What the heck does that all alphabet soup mean?", I give you this short dissertation.

The ABC article says:

"One recent study in the journal Cell described a mutation called D614G in a key protein in SARS-CoV-2, and found it was becoming more common as the pandemic progressed."

But the Cell article it cites seems to say the opposite:

cell.com/cell/fulltext/S009...

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus

"Highlights

•

A SARS-CoV-2 variant with Spike G614 has replaced D614 as the dominant pandemic form

•

The consistent increase of G614 at regional levels may indicate a fitness advantage

•

G614 is associated with lower RT PCR Cts, suggestive of higher viral loads in patients

•

The G614 variant grows to higher titers as pseudotyped virions"

It's a dyslexic nightmare! D614D vs G614 vs D614,

The problem is in understanding the nomenclature.

Scientists get hand cramps easily, so they abbreviate. Then they abbreviate the abbreviations.

614 is the position of the codon (the 3 RNA nucleotide molecules) in the spike protein. It's like a street address, where Spike is the street, and 614 is the house. The G or D are the style of house.

But what does G614D mean?

varnomen.hgvs.org/recommend...

'Format: “prefix”“amino_acid”“position”“new_amino_acid”, e.g. p.(Arg54Ser)

“prefix” = reference sequence used = p.

“amino_acid” = reference amino acid = Arg

“position” = position amino acid subtituted = 54

“new_amino_acid” = new amino acid = Ser'

More decoding of shorthand:

hgmd.cf.ac.uk/docs/cd_amino...

Codon-Amino Acid Abbreviations

There are 3 letter abbreviations, and for the truly cramped, 1 letter abbreviations. They couldn't use the 1st leter of the amino acid, because so many have the same 1st letter.

D = Asp (Aspartate, aka Aspartic Acid)

G = Gly (Glycine)

So D614G means that G replaces the D. There is no prefix in this case.

D614G then means the same as G614.

Nothing could ever go wrong with a notation method like this, right?

And what about vaccines?

It turns out that 614 is not involved in binding the virus to the ACE2 receptor - it's not part of the RBD (receptor binding domain). One aim of vaccines is to block infection by preventing this binding.

This is the best written article I've found on all of this:

news-medical.net/health/D61...

D614G Mutation

"D614G mutation is characterized by aspartic acid to glycine shift at the amino acid position 614 of a protein. Recent studies have shown that D614G mutation in the spike protein of novel coronavirus makes it more infectious, transmissible, and deadly.

"

...

"Could D614G mutation impact vaccine development?

However, there is evidence suggesting that the possibility of D614G mutation affecting the vaccine efficacy is very less. Because the mutation is not in the receptor-binding domain of the spike protein, it is less likely to affect the ability of the domain to induce host immune responses, which is believed to be a prerequisite for antibody-mediated neutralization of the virus.

Moreover, a large portion of ongoing vaccines are developed against the receptor-binding domain, and thus, D614G mutation is not supposed to have any effect on vaccine efficacy.

Another important observation is that convalescent sera obtained people infected with D614 containing viruses have been found to neutralize viruses containing G614, and vice versa. This indicates that D614G mutation does not alter antibody-mediate immune responses. "

=seymour=

[bennevisplace in reply to SeymourB]

Seymour, thanks for the additional insights.

To be fair to ABC, a national broadcaster not a science journal, this was a news bulletin intended to set the record straight in response to a lot of scare stories and other misinformation out there. To your TLDR I would add:

One of many mutations to the virus, D614G is interesting because it's on the spike protein that enables the virus to get inside our cells.

It's suspected that this mutation makes the virus more transmissible, but not that it leads to more severe disease.

It's also unlikely to change the effectiveness of vaccines designed to stimulate antibodies to the virus.

But I think most of us here would be able to cope with the full article.

[bkoffman CLL CURE Hero]

Thanks

[LeoPa]

I saw an interview with a Czech evolutionary biologist who said it is very important to slow the spread of the virus as it gives it more time to mutate towards a less deadly strain. The logic behind it is that a particularly deadly strain kills the infected person before he has time to infect someone else (when everybody is isolated/wears a mask/social distances or combination of these measures). Thus only the less deadly strains are able to spread (which don't cause severe symptoms, don't kill the patient quickly, and thus give him much more time to infect a few others). It sounds completely logical, and the fact that cases are on the rise but the death rate is not yet rising proportionately, at least in Europe, seems to prove it. However when people ignore precautions en masse, the situation can quickly reverse as more deadly mutations get a chance to spread as well. This is what I am afraid of. Human stupidity is our biggest problem. I see too many people getting complacent, wearing face masks as a mouth or chin guard instead of covering their faces properly, including their noses. But it is just as important now as earlier, to slow the spread of the virus as much as possible.

[bennevisplace]

That's a theory that hadn't occurred to me. I'm not sure I buy it though. A virus can be "less deadly", or more deadly, for various reasons. Your biologist's theory demands that it kills or at least disables its victims so swiftly that the mutation(s) have dramatically shortened the incubation period between infection and symptoms. Isn't this conjuring up a very different pathogen like in The Andromeda Strain? From what I've read - admittedly not much - the "successful" mutations like D614G, which appears to be displacing D614 as the dominant form, are those that confer a "fitness benefit", i.e. help the virus to survive rather than make it more or less deadly to its host.

The ~1/3 reduction in mortality rate per hospital case since the early phase of the pandemic is a global phenomenon attributable to improved treatment of severely ill patients. If there are other factors but I have seen no evidence of them.