Emmanuel Profile picture
Sep 23 13 tweets 3 min read Twitter logo Read on Twitter
The TRILOGY that changes the face of the pandemic :

VIROPORIN, ION CHANNELS, MUTATION T9I in the E PROTEIN Image
2) We recently covered these 3 topics, once again. First of all, viroporins.
3) Then very recently the ion channels and the key role of the envelope protein.
4) Concerning the E:T9I mutation, we have addressed this subject several times, showing that it has changed the game with the Omicrons, and then with the mutation E:T11A for the XBBs.
5) We would like to return to this trilogy of viroporin, ion channels and E:T9I mutation, with a study that we will not publish (to avoid unnecessary reactions) but from which we will quote extracts.
"The envelope protein of SARS-CoV-2 (2-E) forms a homopentameric cation channel Image
6) ...that is important for viral pathogenicity. Our previous study demonstrated that the E- protein alone is sufficient to induce cell death, provoke a cytokine storm, and even cause acute respiratory distress syndrome-like damage in vivo."
7) "The allele frequency of the mutation T9I (threonine to isoleucine) in all statistical samples was higher than 99.49%."
"T9I in the envelope protein of the SARS-CoV-2 Omicron variant changes channel properties and attenuates virus production and virulence"
8) "The results revealed that the ion selectivity of T9I mutant channels is different from that of WT channels." (Fig.1C and D)
"Compared with exogenous expression of the WT protein, exogenous expression of the T9I mutant significantly attenuated the viral load (Fig. 1H). Image
9) "As shown in Figure 1I, in comparison with that of WT, the cytotoxic ability of T9I was approximately 150-fold lower, as was cytokine production."

To sum up, "the reduced potassium efflux and additional chloride influx mediated by T9I channels ...
10) ...cause less severe ionic dyshomeostasis, membrane disruption, and lysosome-related cell death."

This doesn't mean that Omicron is less dangerous but its pathogenicity is very different from the previous VOC.
11) The almost exclusive discourse on Spike and immune escape mutations, the virtual refusal to take into account the changes in pathogenicity with the E:T9I mutation in Omicrons and E:T11A in XBBs, the failure to take into account the absence of the E:T11A mutation ...
12) ... of the XBB in BA.2.86, which brings its pathogenicity to the level of the first Omicrons, all this has not facilitated a clear discourse on a pandemic, which has changed its face.
13) Thanks for reading 🙏

FYI
@siamosolocani @SystemsVirology @shay_fleishon @mrmickme @DavidJoffe64 @arijitchakrav @HarrySpoelstra @C_A_Gustave @outbreakupdates @GourlaySyd @_ppmv @AltenbergLee @UseBy2022 @RolandBakerIII

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More from @ejustin46

Sep 22
PATHOGENESIS.
VIROPORIN, one of the best WEAPONS of SARS-COV-2, to kill CELLS ! Image
2) SUMMARY
Viroporins are a class of small viral proteins that can alter the permeability of cellular membranes, allowing ions and molecules to pass through. They can disrupt ion homeostasis and calcium signaling pathways within infected cells. This disruption can lead ... Image
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IMMUNE IMPRINTING !

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2) "Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting"


Key findings :

▶️ "Immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters"biorxiv.org/content/10.110…
3) ▶️ Single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB"
▶️ "Repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers ...
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"We discovered that SARS-CoV-2 infection leads to a prolonged alteration of the gene expression profile of circulating T, B and NK cells and monocytes" 😨
genomemedicine.biomedcentral.com/articles/10.11…
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2) The IL-2-induced anti-inflammatory gene expression signature (IL2-AIS) score is progressively decreased after SARS-CoV-2 infection Image
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