Potentially neurotoxic SARS-CoV-2 protein fragments – News-Medical.net
The severe acute respiratory syndrome coronavirus 2 (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.
In addition to these adverse effects of COVID-19, many patients will also report neurological symptoms such as…….
The severe acute respiratory syndrome coronavirus 2 (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.
In addition to these adverse effects of COVID-19, many patients will 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 suffering from ‘long COVID,’ where the symptoms persist long after the initial infection.
Study: Neurotoxic Amyloidogenic Peptides Identified in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19. Image Credit: Kateryna Kon / Shutterstock.com
In a recent study published on the preprint server bioRxiv*, researchers from La Trobe University investigate 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.
About the study
In the current study, the researchers 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.
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.
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. TANGO plots for ORF-10 shows that the main aggregation-prone sequence is residues F11TIYSLLLC; however, this was not confirmed by ZIPPER.
Next, the researchers 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 scientists then decided to synthesize and investigate RNYIAQVD and ILLIIM.
Study findings
Atomic force microscopy (AFM) and transmission electron microscopy (TEM) imaging shows both peptides can assemble into needle-like crystalline assemblies in as little as two hours at significant concentrations. 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.
ILLIM varies between 4-9 nanometers (nm) tall, while RNY1AQVD is an average height of 5.5 …….
Source: https://www.news-medical.net/news/20211130/Potentially-neurotoxic-SARS-CoV-2-protein-fragments.aspx
