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
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).
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.
PATHOGENESIS.
VIROPORIN, one of the best WEAPONS of SARS-COV-2, to kill CELLS !
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 ...
... to the activation of inflammatory responses and contribute to the pathogenesis of COVID-19. Additionally, the viroporin may affect cellular signaling cascades and modulate host immune responses, potentially aiding the virus in evading host defenses.
2) First a wonderful study about
"Genetic architecture of the white matter connectome of the human brain"
Polygenic dispositions to various brain-related disorders or behavioral traits show multivariate associations in 30,810 participants science.org/doi/10.1126/sc…
"Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics." biorxiv.org/content/10.110…
2) ACE2-VLPs produced using the psPAX2 plasmid lentiviral packaging system bearing full length ACE2 protein had the highest pseudovirus neutralization activity
3) ACE2-VLPs and ACE2-EVs were successfully characterized and purified.
▶️ "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 ...
"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…
2) The IL-2-induced anti-inflammatory gene expression signature (IL2-AIS) score is progressively decreased after SARS-CoV-2 infection
3) NF-kB is associated with the regulation of the transcriptional alterations of IL2-AIS genes in COVID-19 patients