Study Reveals SARS-CoV-2 Also Binds With STRA6 Receptors, Providing Explanation For Symptoms And Long COVID Conditions With Unknown Aetiology!

SARS-CoV-2 Research: A study by researchers from Damietta University-Egypt, Kafrelsheikh University-Egypt, Mahala Hepatology Teaching Hospital-Egypt, Federal University of Alfenas-Brazil, Al Azhar University-Egypt and the Ministry of health-Saudia Arabia has found that the SARS-CoV-2 virus is also able to bind with the STRA6 receptors found in the human host to gain entry in to neurons, immune cells and also other cell types.


 
This SARS-CoV-2 Research discovery could provide explanations as to why the olfactory neurons could be infected during SARS-CoV-2 infections leading to anosmia or also as to why it has been found that lymphocytes are often destroyed by the SARS-CoV-2 virus.
 
Already it has been known that besides the ACE-2 receptors, the SARS-CoV-2 virus is also able to use a variety of other human host receptors to gain cell entry. From Thailand Medical News’ research database, these receptors include CD147, Neuropilin‐1, Dipeptidyl peptidase 4, alanyl aminopeptidase (ANPEP), glutamyl aminopeptidase (ENPEP),angiotensin II receptor type 2 (AGTR2), AXL, ASGR1, KREMEN1, Heparan Sulfate, DCL-SIGN, L-SIGN, MR, MGL, Nicotinic acetylcholine receptors via gp120 motif, Low Density Lipoprotein Receptor Protein 1 (LRP1), LFA-1 receptors and also endosomal proteases like Cathepsin L and B.
 
It is very important for credible scientist and doctors promoting therapeutic solutions for COVID-19 and also Long COVID to truly understand and know all these along with how various cellular pathways are being affected, which host genes and proteomes are being dysregulated and also to monitor protein mutations in the emerging SARS-CoV-2 variants. Many charlatans from entities like the FLCCC, Vejon Health, The Long COVID-19 Foundation-Leeds and individuals like Dr Zelenko simply have superficial knowledge and yet are promoting bogus therapeutic and prophylactic protocols! The same applies to ‘experts’ from the agencies like the U.S FDA, U.S. CDC and U.S. NIH and even certain groups in the WHO along with the scammers from some of the big American and European pharmaceutical agencies!
 
The integral membrane receptor STRA6 mediates cellular uptake of vitamin A by recognizing RBP-retinol to trigger release and internalization of retinol. It is originally characterized in cancer cells as a retinoic acid stimulated gene. The receptor is found in endometrial stromal cells, syncytiotrophoblasts, club cells, fibroblasts, extravillous trophoblasts, proximal tubular cells and also in certain cells of the testis and olfactory neurons and other components of the immune system. https://www.proteinatlas.org/ENSG00000137868-STRA6
 
https://deepblue.lib.umich.edu/bitstream/handle/2027.42/150188/Barrett2019.pdf?sequence=1
 
https://www.sciencedirect.com/science/article/pii/S0925477397000397 a>
 
https://www.researchgate.net/figure/Expression-of-Rdh10-in-the-developing-olfactory-system-and-vibrissae-follicles-The_fig2_5452256
 
The study findings from this new research showed that COVID-19 Spike protein exhibited a high binding affinity for human STRA6 and a low binding energy with it. The docking score of COVID-19 spike protein with STRA6( -354.68) kcal/mol was higher than the docking score of spike protein with ACE2((-341.21 ) kcal/mol.
 
The findings showed that the spike protein Receptor Binding Domain (RDB) of COVID-19 strongly and efficiently   binds to STRA6 receptor, definitely to the RDB vital residues of RBP-binding motif located in STRA6 receptor. The docking of STRA6 target protein with spike viral protein revealed the involvement of the spike protein into the extracellular and membrane part of the STRA6 receptor and amino acids residues of STRA6 along with spike protein which make interactions and play an important role in formation of complexes.
 
The findings showed that the corresponding distances about the residue contacts between proteins STRA6- Spike protein complex are documented here where the STRA6- Spike protein complexes binding site are the RDB of the CHOLESTEROL in STRA6 receptor which bind with interface residue( ARG   511A , VAL   512A    THR   515A    ALA   516A    ASN   519A with interface residue degree (2.965 , 3.595 , 3.286 , 4.592 , and 4.235) representatively, also the ability of the spike to bind to RDB of the STRA 6 protein in the ILE   131C    , MET   145C    , HIS    86A with interface residue( 4.961 , 4.953 and 3.271) representatively. STRA6- Spike protein complex with PDB ID (5SY1 , 6LZG) representatively ,the chain A ,B with Align – length ( 582 ,194 ) then the quarry coverage of proteins 0.793 and 1.000 with sequence identity 96.2 % and 100,0 % representatively. The surface view of complex reveals that the binding pocket of STRA6- Spike protein and Spike ACE 2 complexes with RMSD (189.44 Å , 1.00 Å ) representatively and docking score (-341.21 ,-354.68)  kcal/mol, the quality of the receptor and the ligand are LGscore and MaxSub ( 2.416 , 0.147 ) where the structure are correct representatively for the STRA6 receptor protein, and LGscore and MaxSub ,(5.056 ,0.217).
 
The STRA6 receptor is a critical regulator of many biological processes thorough initiating cellular retinol uptake, in different organs and tissues as in immune cells for improving the immune system homeostasis in various populations.
 
This new docking study reveals that COVID-19 spike protein binds directly to the integral membrane receptor (STRA6) in addition to its binding sites of the cholesterol. STRA6 mediates cellular uptake of retinol (vitamin A) by recognizing a molecule of RBP-retinol to trigger release and internalization of retinol.
 
Hence COVID-19 may leads to downregulation of STRA6 receptor leading to inhibition of the regulatory function of retinoic acid and cholesterol, contributing to existing of infection phase and Long COVID symptoms and complications including lymphopenia, neurological disorders, disrupted RIG-I pathway, interferon inhibition, cytokine storm initiation, diabetes, hormonal imbalance, thrombosis, and smell loss.
 
The study team believes that this novel discovery that STRA6 receptor acts as a novel binding receptor for COVID-19 could explain many previously unexplained pre and post-covid-91 infection symptoms.
 
Furthermore, retinoic acid metabolism was found to be defective in COVID-19 (cytokine storm), sepsis, ARDS and SIRS.
 
The study team proposes that reconstitution of the retinoid signaling may prove to be a valid strategy for COVID-19 management.
 
Hence, they suggest that certain Vitamin A metabolites, especially, retinoic acid will be promising and effective treatments for COVID-19 infection and its unknown aetiology symptoms.
 
Currently aerosolized all- trans retinoic acid and 13 cis retinoic acid is currently under clinical investigation (ClinicalTrials.gov Identifier: NCT05002530, NCT04353180) https://clinicaltrials.gov/ct2/show/NCT05002530
https://clinicaltrials.gov/ct2/show/NCT04353180
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.researchsquare.com/article/rs-936697/v1
 
Thailand Medical News would further like to add that for the treatment of Long COVID, there is no such thing as a single therapeutic product nor a single protocol! Long COVID has to be treated from a personalized precision medicine approach where after symptoms have been collated, specific diagnostic and imaging test are carried out to ascertain what cellular pathways, cells, tissues and organs along with genes and proteases have been affected by the SARS-CoV-2 and along with the identification of the variants at play. Only then can various developed therapeutics products be dispensed.
 
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