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BREAKING NEWS
Source: Omicron Research  Jan 17, 2022  2 years, 2 months, 1 day, 15 hours, 23 minutes ago

BREAKING! Omicron Will Wreak Havoc On Your Body Weeks Later As It Can Bind To Cells Using Cellular Polyanionic Receptors Like Heparan Sulfate!

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BREAKING! Omicron Will Wreak Havoc On Your Body Weeks Later As It Can Bind To Cells Using Cellular Polyanionic Receptors Like Heparan Sulfate!
Source: Omicron Research  Jan 17, 2022  2 years, 2 months, 1 day, 15 hours, 23 minutes ago
Omicron Research: The future of the world population is definitely in jeopardy now as many were led to believe that Omicron is mild although highly transmissible and infectious. The fallacy arose as result of half-baked data from certain incompetent professionals in South Africa who just wanted instant fame on media. And many other so-called medical experts from elsewhere were stupid to have believed them and made premature assumptions and comments publicly.

 
Interestingly, one of the very few distinguished and credible professionals in South Africa, Dr Ridhwaan Suliman, a senior researcher at CSIR has been monitoring and tweeting the increasing death rates weeks after the Omicron surge in South Africa!
 
https://twitter.com/rid1tweets/status/1482997458225573890
 
https://twitter.com/rid1tweets/status/1481889683969822721
 
As a result a large percentage  of the ignorant masses being lax as they were publicly misinformed via the Western mainstream media by so called ‘experts’ that the Omicron was mild, we are now seeing more than an average of 3 million new COVID-19 infections per day over the last 5 days and hospitalizations are also hitting record levels in most countries. Global death rates are also hovering about an average of more than 8,000 deaths per day. https://www.worldometers.info/coronavirus/
 
These death rates are expected to increase exponentially in coming weeks if things were to emulate what had happened and is happening in South Africa!
 
Despite many being asymptomatic or only having mild symptoms upon an infection with the Omicron variant, it is even more important to know what is happening to them down the road…weeks, months and years later.
 
From preliminary understanding of the way the Omicron works and its pathogenesis, trust us, the world is literally ‘screwed’! (Pardon us for the language!).
 
We already knew that the Omicron was moving away from the ACE-2 receptor but what we did not know that besides the possibility it was using other receptors like DDP4 and even neuropilin1 and also using Cathepsins for cell entry via endosomal fusions, we never knew or thought that it could find other ways to bind to the human host cells! (A shift from the ACE-2 receptor to other receptors or even using other methods to enhance its binding to the ACE2 receptor could mean that it is affecting the human host in many new and different ways and could be gradually attacking other tissues and organs silently which could lead to a variety of medical and health conditions manifesting itself later, some of which could have fatal outcomes!
 
https://www.thailandmedical.news/news/breaking-omicron-has-shifted-to-using-cathepsins-for-cell-entry-via-endosomal-fusion,-impacting-cellular-tropism-and-pathogenesis
 
ron-might-not-affect-lungs-much,-rather-your-brains,-heart-and-other-organs-are-targets">https://www.thailandmedical.news/news/good-news-preliminary-unpublished-data-shows-that-omicron-might-not-affect-lungs-much,-rather-your-brains,-heart-and-other-organs-are-targets
 
https://www.thailandmedical.news/news/breaking-study-alarmingly-shows-omicron-could-be-possibly-evolving-to-shift-its-focus-on-human-receptors-from-ace2-to-ddp-iv,-similar-to-mers
 
https://www.researchsquare.com/article/rs-1247982/v1
 
A new study by German researchers from Freie Universität Berlin and Max Planck Institute has alarmingly found that the Omicron variant is capable of binding to human host cells simply by using a variety of cellular polyanionic receptors including heparan sulfate!
 
This new Omicron Research findings is a game changer and shows that the pathogenesis of the  Omicron variant could be totally different from all other SARS-CoV-2 variants known so far and if Thailand Medical News’ hypothesis is right in that we will see more worrisome medical conditions arising in individuals who were infected with the Omicron variant weeks and months later, despite being asymptomatic or only having mild symptoms initially.  Many of these new medical conditions are going to end in fatal consequences including strokes, heart failures, cerebral venous sinus thrombosis (CVST), acute kidney injury, brain and CNS damage, liver damage, cancers and sepsis due to gastro intestinal issues, secondary opportunistic infections due to a dysregulated immune system and immunodeficiency, just to name a few.
 
To date, evidence is strengthening that the novel SARS-CoV-2 mutant Omicron, with its more than 60 mutations, will spread and dominate worldwide.
 
Despite the mutations in the spike protein are known, the molecular basis for why the additional mutations in the spike protein that have not previously occurred account for Omicron's higher infection potential is not fully understood. 
 
The study team proposed based on a chemical rational that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs. wild type) increases binding to cellular polyanionic receptors, such as heparan sulfate due to multivalent charge-charge interactions.
 
The study findings were published in the peer reviewed journal: ChemBioChem.
https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202100681
 
The study findings propose that the elevated occurrence of positively charged amino acids in specific domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spike protein improves viral binding to cellular negatively charged receptors aiding in enhanced infectiousness.
 
The SARS-CoV-2 coronavirus, due to its high mutation potential, has given rise to several mutants accompanied by increased viral fitness and enhanced viral infectivity compared to the wild type. As a result, these new variants quickly replaced the previously prevailing mutants all across the globe.
 
The most recent SARS-CoV-2 variant, Omicron, contains more than 60 genetic mutations compared to wild type and the related reports indicate an even enhanced infectivity.
 
The study team, therefore, conducted the current study based on chemical modeling and simulations to understand how these mutations would alter the interaction of the Omicron variant with the host cells of the respiratory tract.
 
The study findings showed that the first step for SARS-CoV-2 entry into the cell is the interaction of virus spike with the heparan sulfate proteoglycans (HSPG), a proteoglycan polysulfate on the cell surface, even before interacting with cellular ACE2 receptor. The HSPG consists of unbranched, negatively charged heparan sulfate (HS) attached to cell surface proteins.
 
Past studies had suggested that the initial binding is related to the electrostatic interaction between anionic HSPG and cationic patches on the viral proteins. https://pubmed.ncbi.nlm.nih.gov/31266258/
 
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7894192/
 
Importantly, the fact that the electrostatic interactions could drive the initial interaction of the virus with the host cells has mostly been underscored by most recent studies that mainly focus on viral interaction with the host ACE2 receptor.
 
A study that involved enzymatic removal of the HSPG from cell surfaces showed a significant reduction in the SARS-CoV-2 infection. https://pennstate.pure.elsevier.com/en/publications/sars-cov-2-infection-depends-on-cellular-heparan-sulfate-and-ace2
 
Furthermore, highly charged electrolytes have also been shown to compete and block the initial interaction of HSPG with the virus. These reports clearly suggest the role of initial electrostatic interaction between viruses and the host cells. https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202102717
 
The study team on analyzing all 32 mutations in the spike sequence Omicron variant, found that the positive charge increased by +9 in the altered amino acid sequence of the Omicron variant, compared to the wild type SARS-CoV-2.
 
Interestingly, the previous mutational event leading to the emergence of the Delta variant was associated with an increase of +4 positive charge. The conservation and enrichment of such mutations in virus variants strongly indicate a selective advantage in initial binding to the host cell.
 
Detailed electrostatic potential mapping shows the location of the cationic patch at some distance away from the receptor-binding motif (RBM) in wild-type RBD. In Delta variant RBD, this cationic patch becomes larger because of the two charged mutations L452R and T478K.
 
In the same way, in Omicron RBD, in addition to this patch, a new cationic patch is formed (located right on the RBM) due to three neighboring charged mutations (Q493R, Q498R, and Y501H). Thus, the new variant is expected to bind more strongly to the negatively charged HSPGs present on the cell surface.
 
The study team confirmed this hypothesis using simulations of all-atom molecular dynamics (MD). Since Omicron is modified to own two cationic patches on RBD, the polyglycerol sulfate can bind to these two positions bestowing an improved binding affinity on the Omicron variant, and therefore more infectiousness.
 
Also, it is known that mutation P681R has been shown to facilitate furin-mediated cleavage of the spike protein in the Delta variant. Furin enzyme from the host organism cleaves the spike protein into the S1 and S2 subunits and primes fusion of the virus envelope with the host cell membrane.
 
The study team observed a similar mutation P681H, next to the -RRAR- furin cleavage site of the Omicron variant that might signal towards another modification for an enhanced infection potential of Omicron.
 
The study team suggests more experimental studies will be needed to characterize the consequences of the mutation P681H in the Omicron variant.
 
The study team also hints towards the possibility of other mutations in Omicron RBD, which may enhance the second step of binding, i.e., its interaction with the ACE2 receptor. This is because certain mutations in the RBM (such as K417, S477, T478, E484, and N501) that have been shown to enhance viral binding to ACE2, are also present in the Omicron RBM.
 
The study team concluded, “Based on a chemical rational that the elevated occurrence of positively charged amino acids in certain domains of the spike protein (Delta: +4; Omicron: +5 vs. wild type) increases binding to cellular polyanionic receptors, such as heparan sulfate due to multivalent charge-charge interactions, this observation is a starting point for targeted drug development.”

It should be noted that past studies have already showed that viruses by binding to the various host cellular polyanionic receptors like heparan sulfate can cause various long-term medical issues as these polyanionic receptors like heparan sulfate are also crucial for other various cellular processes and pathways.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6669472/

https://www.frontiersin.org/articles/10.3389/fmolb.2020.628551/full

For the latest Omicron Research, keep on logging to Thailand Medical News.
 
Read Also: https://www.thailandmedical.news/news/warning-omicron-is-still-evolving-the-world-will-pay-dearly-for-assuming-it-is-mild-
 
https://www.thailandmedical.news/news/breaking-study-shows-that-breakthrough-covid-19-infections-increase-risk-of-health-problems-and-mortality,-contrary-to-common-assumptions
 
https://www.thailandmedical.news/news/morons-having-initial-mild-symptoms-from-a-viral-infection-does-not-mean-things-are-good-omicron-spreading-rapidly-across-the-globe-uk-the-next-hotspo
 
 
 

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