We Apologies For Any Inconveniences As The Site Is Having Some Technical Changes Done With New Modules Coming Soon

BREAKING NEWS
Source: Medical News - SARS-CoV-2 Research  Dec 01, 2021  2 months ago
BREAKING! SARS-CoV-2 Contains Amyloidogenic Peptide Fragments That Are Neurotoxic To Human Hosts!
BREAKING! SARS-CoV-2 Contains Amyloidogenic Peptide Fragments That Are Neurotoxic To Human Hosts!
Source: Medical News - SARS-CoV-2 Research  Dec 01, 2021  2 months ago
A new study by researcher from La Trobe University-Australia, Swinburne University of Technology-Australia, ETH Zurich University -Switzerland and the University of Luxembourg has shockingly found that SARS-CoV-2 protein fragments themselves possess neurotoxic properties and are dangerous for the human host. These amyloidogenic peptides are capable of causing a variety of neurological issues in the human host.


Even after so called deemed ‘recovery’, circulating amounts of these protein fragments are still being found in individuals and are able to keep on causing these neurological damages.

The study findings are alarming as it implies a variety of scenarios in terms of what we can expect to see months and years down the road in those that had been infected with the SARS-Cov-2 virus. Ever growing and deteriorating neurological issues are going to be a strain on the public healthcare infrastructures in countries across the world.
 
Despite COVID-19 primarily known as being a respiratory disease caused by the virus SARS-CoV-2, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’ or PASC).
 
These neurological symptoms are thought to be caused by brain inflammation, triggered by the virus infecting the central nervous system of COVID-19 patients, however the mechanisms for these symptoms have never been fully understood.
 
The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature.
 
Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology the study team performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic.
 
The study team selected two of these peptides and discovered that they do rapidly self-assemble into amyloid.
 
Alarmingly, these amyloid assemblies were shown to be highly toxic to a neuronal cell line.
 
The study findings introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID, especially those symptoms which are novel to long COVID in contrast to other post-viral syndromes.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2021.11.24.469537v1
 
The SARS-CoV-2 which is the virus responsible for the coronavirus disease 2019 (COVID-19), primarily targets respiratory organs, as it reproduces in, and subsequently damages and kills, these epithelial cells. This leads to widespread inflammation and immune dysfunction, including issues such as cytokine storms.
 
Besides these many adverse effects of COVID-19, many patients also report neurological symptoms such as memory loss, mental health issues, as well as cognitive and psychiatric disorders. These are most commonly reported in patients su ffering from 'long COVID,' where the symptoms persist long after the initial infection.
 
The study team led researchers from La Trobe University investigated the potentially amyloidogenic peptide fragments that could be neurotoxic in an effort to explain some of the neurological symptoms associated with COVID-19 and long-COVID.
 
The study team used two different algorithms to predict peptide sequences that showed a tendency to form beta-rich amyloid assemblies. TANGO is an algorithm used to predict aggregation nucleation regions in unfolding polypeptide chains, assuming that the aggregating regions are within the hydrophobic core, while ZIPPER predicts hexapeptides within larger polypeptide sequences.
 
Interestingly when the ZIPPER tool was applied to open reading frame 6 (ORF-6), it showed more than ten choices of six-residue windows. These were narrowed down by also using the TANGO algorithm, which left two regions predicted to be highly aggregation-prone, of which include I14LLIIMR and D30YIINLIIKNL.
 
The peptide ILLIIM was chosen as the first candidate, as it closely resembles a sequence from Hen Egg White Lysozyme, which has also been seen to be highly amyloidogenic.

Cytotoxicity assays of RNYIAQVD and ILLIIM assemblies over a range of concentrations. Error bars represent 1 Standard Deviation. Statistical analysis performed by one way ANOVA with Tukey comparison. N.S. = No statistical significance, ** = p < 0.0005, *** = p < 0.0001.

Subsequent TANGO plots for ORF-10 shows that the main aggregation-prone sequence is residues F11TIYSLLLC; however, this was not confirmed by ZIPPER.
 
The study team next chose the octapeptide R24NYIAQVD due to its zwitterionic residue pair R-D, which appears to strongly enhance interpeptide association. A hexapeptide within RNYIAQVD was also predicted to be highly amyloidogenic by ZIPPER.
 
The study team then decided to synthesize and investigate RNYIAQVD and ILLIIM.
 
Utilizing atomic force microscopy (AFM) and transmission electron microscopy (TEM) imaging showed that both peptides can assemble into needle-like crystalline assemblies in as little as two hours at significant concentrations.
 
Interestingly both peptides tend to stack on top of each other in order to form multilaminar nonfibrillar structures, which occurs more often in RNY1AQVD than in ILLIIM.
 
The peptide ILLIM varies between 4-9 nanometers (nm) tall, while RNY1AQVD is an average height of 5.5 nm. ILLIIM is also very wide at around 2-3 microns in length.
 
Detailed statistical analysis of fibril widths and contour lengths revealed that both peptides show a heterogeneous distribution of fibril widths and a biphasic distribution of lengths, with two broad sub-populations centered around 1 and 3 micrometers (µm).
 
The amyloid nature of the two assemblies was further confirmed by wide angle X-ray scattering (WAXs) spectra, with both peptides possessing a number of strongly diffracting Bragg peaks, including a characteristic peak at 1.38A-1, which corresponds to a d-spacing of A that is indicative of amyloid assembly from extended beta-sheets.
 
The study team stress that their hypothesis that these two viral transcript fragments are toxic to human neurons is supported by their findings.
 
Importantly this neurotoxic potential is corroborated by previous reports on the neuroinvasive capabilities of SARS-CoV-2, coupled with the similarities of the symptoms to Alzheimer's disease and the previous detection of any amyloid assemblies driven by other viruses.
 
Detailed cytotoxic assays of the two peptides against a human-derived neuroblastoma cell line (SH-SY5Y) revealed that both assemblies were highly toxic after 48-hour incubation with the target peptide. Concentrations as low as 0.05/0.04 millimolar (mM) were seen to kill over 50% of the cell lines, which are often used as a model cell line for studying neurodegenerative disorders.
 
The study team urge further investigations into the presence of amyloid aggregates from SARS-CoV-2 in the central nervous system (CNS) of COVID-19 patients and suggest that these may be responsible for some of the neurological symptoms observed in these patients.
 
Corresponding author, Dr Joshua T. Berryman from the Department of Physics and Materials Science, Faculty of Science, Technology and Medicine, University of Luxembourg told Thailand Medical News, “This would explain some of the symptoms seen in 'long COVID,' in which patients suffer a wide variety of symptoms, including long-term anosmia, fatigue, depression, anxiety tinnitus, and earaches.”
 
The study findings could help to inform healthcare workers and researchers, as well as possibly lead to a treatment or preventative treatment to help prevent these symptoms from developing in others.
 
Please help to sustain this site and also all our research and community initiatives by making a donation. Your help means a lot and helps saves lives directly and indirectly and we desperately also need financial help now.
https://www.thailandmedical.news/p/sponsorship
 
For the latest SARS-CoV-2 Research, keep on logging to Thailand Medical News.

Please share this article with as many as possible as those controlling the COVID-19 narratives are trying to get us to stop publishing research findings to the general public and are getting the American and British social media platorms and search engines to suppress our news feeds.
 
 

MOST READ

Feb 05, 2020  2 years ago
Source : Thailand Medical news