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Nikhil Prasad  Fact checked by:Thailand Medical News Team Dec 14, 2023  2 months, 1 week, 3 days, 23 hours, 38 minutes ago

COVID-19 News: Russian Study Uncovers Self-Assembling Self-Assembling From SARS-CoV-2 S1, S2, RBD And N Recombinant Proteins!

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COVID-19 News: Russian Study Uncovers Self-Assembling Self-Assembling From SARS-CoV-2 S1, S2, RBD And N Recombinant Proteins!
Nikhil Prasad  Fact checked by:Thailand Medical News Team Dec 14, 2023  2 months, 1 week, 3 days, 23 hours, 38 minutes ago
COVID-19 News: In the relentless pursuit of unraveling the mysteries surrounding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers at the Federal Research and Clinical Center of Physical-Chemical Medicine in Moscow, Russia, alongside collaborators from various esteemed institutions, have made a groundbreaking discovery. Their study covered in this COVID-19 News report, delves into the world of self-assembling nanoparticles (saNP) and nanofibers found within recombinant coronavirus SARS-CoV-2 proteins, specifically S1, S2, RBD, and N, raising profound implications for our understanding of the virus and its potential impact on human health.


                                                 Graphical Abstract 

Probing the Nanostructures
The investigation employed sophisticated techniques, including scanning electron microscopy (SEM), atomic force microscopy (AFM), and dynamic light scattering (DLS), to meticulously examine the purified SARS-CoV-2 proteins. The proteins were isolated using affinity chromatography with Ni Sepharose, a process that allowed for the precise examination of the nanostructures.
 
To conduct their research, the team isolated SARS-CoV-2 RNA from the nasopharyngeal swabs of COVID-19 patients in Moscow. This RNA served as the basis for obtaining DNA fragments encoding viral antigens through reverse transcription and PCR techniques. Four recombinant SARS-CoV-2 proteins, namely S1, S2, RBD, and N, were successfully isolated from transformed E. coli cells and human embryonic kidney cell line Expi293F.
 
Remarkably, the researchers uncovered self-assembling nanoparticles and nanofibers of varying sizes. AFM in a liquid cell without surface drying revealed mean sizes of 80.03 nm for S1 saNP and 93.32 nm for S2 saNP. These solid protein structures exhibited stability after enduring multiple freeze-thaw cycles over a span of two years at -20 °C, even in hyperosmotic solutions.
 
Intriguingly, receptor-mediated penetration experiments demonstrated that the SARS-CoV-2 S1 and RBD saNP exhibited more efficient penetration into African green monkey kidney Vero cells, which possess specific receptors for β-coronavirus reproduction, compared to unspecific endocytosis into MDCK cells lacking these receptors.
 
Stability and Affinity Among Structural Proteins
The researchers confirmed the stability of the solid saNP through various analytical methods, including denaturating SDS-PAAG electrophoresis, SEM, AFM, and fluorescent microscopy. Notably, the absence of internal empty spaces in the nanostructures distinguished them from virus-like particles (VLP). The high affinity observed among the SARS-CoV-2 structural proteins provided insights into the rapid formation of these nanostructures.
 
< strong>Amyloid-Like Structures: Unveiling the Hidden Threat
The study took a captivating turn when amyloid-like structures were revealed within the SARS-CoV-2 S1, S2, RBD, and N saNP. Thioflavin T and Congo Red dyes interacted with these structures, exposing their amyloid-like nature. This revelation opens a new avenue of concern, suggesting that the self-assembling nanostructures, induced by the internal affinity of SARS-CoV-2 virion proteins, might contribute to proteinopathy in patients.
 
Implications for Neurological Disorders
The global impact of COVID-19 extends beyond respiratory distress, with at least one-third of patients experiencing neurological symptoms. The ability of SARS-CoV-2 to cross the blood–brain barrier and infect neuronal cells raises concerns about potential neurological sequelae. The study hints at the possibility of amyloid-related neurodegenerative diseases such as Alzheimer's and Parkinson's being linked to the virus-induced nanostructures.
 
Implications for Vaccinology and Diagnostics
The study's findings pose significant implications for both immunodiagnostics and vaccinology. The shielding effect of the solid nanostructures could impact the accuracy of diagnostic systems by concealing structural antigens. In vaccinology, the potential induction of a Th1 immune response through unspecific endocytosis of saNP raises questions about the stability and efficacy of recombinant subunit vaccines.
 
Conclusion
In the ever-evolving landscape of COVID-19 research, the Russian study on self-assembling amyloid-like nanostructures within SARS-CoV-2 proteins marks a pivotal moment. The intricate interplay between these nanostructures and the human body poses challenges and opportunities for understanding the virus's impact on neurological health, diagnostic accuracy, and vaccine development. As the scientific community grapples with these revelations, further investigations will be crucial in advancing our comprehension of the complex interactions between SARS-CoV-2 and the human body.
 
The study findings were published in the peer reviewed journal: Archives of Biochemistry and Biophysics.
https://www.sciencedirect.com/science/article/abs/pii/S0003986123003429
 
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