D614G – No evidence for increased human transmission

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  • Sun, Jul 12, 2020 - 08:20pm

    #1
    tatagiri

    tatagiri

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    D614G – No evidence for increased human transmission

https://www.virology.ws/2020/07/09/no-evidence-for-increased-human-transmission-of-sars-cov-2/ 

 

SARS-CoV-2 virus isolates from many parts of the world have a single amino acid change in the spike protein, D614G. This observation in itself doesn’t mean very much. It could be that the change arose early in the outbreak and as this virus spread to other areas it was maintained because it has no fitness cost. We call this behavior ‘founder effect’. Whether the change has been selected for – what we would call ‘positive selection’, as claimed by many virologists, needs to be proven by experiments that have not been done.

 

  • Mon, Jul 13, 2020 - 10:08am

    #2
    TurquoiseRose

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    D614G – No evidence for increased human transmission

Perhaps he missed this paper ->

D614G mutation in the SARS-CoV-2 spike protein
reduces S1 shedding & increases infectivity by 9X’s compensating for furin cleavage site From Scripps.

https://www.biorxiv.org/content/10.1101/2020.06.12.148726v1.full.pdfV

Viruses with Spike-G614 were 9X’s more infectious in cell culture  than those without the mutation.

Ø  Mutation markedly increased functional spikes on viral surface by 4-5 times.

Ø   Spikes are what allow the virus to bind to + infect cells via ACE2 receptors.

Ø  D614G, provides greater flexibility to the spike’s “backbone” allowing newly made viral particles to navigate from the producer cell to target cell fully intact, with less tendency to fall apart prematurely.

This conserves the S1 piece-> so there are more copies

  • Mon, Jul 13, 2020 - 11:30am

    #3
    tatagiri

    tatagiri

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    D614G – No evidence for increased human transmission

https://www.cell.com/cell/pdf/S0092-8674(20)30817-5.pdf 

 

May be, the evidence so far is in petri dish and from RNA from swabs (dead virus??). we still lack direct evidence.

Will D614G make infections more severe?

So far there is no evidence that infection with SARS-CoV-2 containing the G614 variant will lead to more severe disease. By examining clinical data from 999 COVID-19 cases diagnosed in the United Kingdom, Korber et al. (2020) found that patients infected with viruses containing G614 had higher levels of virus RNA, but not did not find a difference in hospitalization outcomes. These clinical observations are supported by two independent studies: 175 COVID-19 patients from Seattle, WA (Wagner et al., 2020) and 88 COVID-19 patients from Chicago, IL (Lorenzo-Redondo et al., 2020). Viral load and disease severity are not always correlated, particularly when viral RNA is used to estimate virus titer. The current evidence suggests that D614G is less important for COVID-19 than other risk factors, such as age or comorbidities.

  • Mon, Jul 13, 2020 - 11:57am

    #4
    TurquoiseRose

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    D614G – No evidence for increased human transmission

Reply to tatagirl RE:  D614G – No evidence for increased human transmission

ORF3c has a new stop codon hitchhiking with Spike-D614G the dominant strain “G“ Clade

https://www.biorxiv.org/content/10.1101/2020.05.21.109280v1.full.pdf

Do OLG’s (Overlapping genes) Increase transmissibility?

ORF3c ->predicted protein of 238 amino acids; a membrane protein with 3 transmembrane regions.

ORF3c gained a new stop codon (G25563U) that rose in frequency; 401 sequenced samples demonstrate this mutation in multiple hosts.

New ORF3c stop codon hitchhiked early with haplotype 241U/3037U/14408U/23403G (Spike-D614G), ->drives European + world spread.

Results liken ORF3c to other important viral accessory genes recombined, lost, split, or truncated before or during outbreaks, including ORF3b + ORF8.

OLGs deserve considerably more attention, their rapid evolution may be more important than is currently appreciated in the emergence of zoonotic viruses.

Epistatic network in SARS-CoV-2 genome

https://www.biorxiv.org/content/10.1101/2020.04.10.035964v1.full.pdf

Another concept harder to ferret out-  Do neighboring genes affect each other?

Coevolving pair codons
involving sites evolving under positive selection at different regions of SARSCoV-2 genome are shown with stars, suggesting selection of these sites may be the result of epistasis (Neighboring genes affecting each other).

 

 

  • Tue, Jul 14, 2020 - 06:50pm

    #5
    Dr. Jurgen Mayer

    Dr. Jurgen Mayer

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    D614G – No evidence for increased human transmission

TurquoiseRose is 100% correct. We would not expect this mutation to increase human to human transmission of the virus. We expected it would make the virus more virulent, which was confirmed, months ago to be the case.

The G clade was first detected on January 28th in Germany (EPI ISL 450198). More importantly, as TurquoiseRose somewhat pointed out is that we have two piggyback clades stemming from the G. These are known as GR and GH

 

GH = S-D614G + NS3-Q57H

GR = S-D614G + N-G204R

This virus absolutely has no need to increase human transmissions when it can already destroy every organ in the host body..

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