Tag: peptides

An amyloidogenic fragment of the SARS CoV-2 envelope protein promotes serum amyloid A misfolding and fibrillization

Abstract:

SARS CoV-2 infection can affect a surprising number of organs in the body and cause symptoms such as abnormal blood coagulation, fibrinolytic disturbances, and neurodegeneration. Our study delves into the intricate pathogenic potential of a SARS-CoV-2 envelope protein peptide, shedding light on its implications for multi-organ effects and amyloid formation. Specifically, we focus on the peptide SK9 or 54SFYVYSRVK62 derived from the C-terminus of human SARS coronavirus 2 envelope protein.

We demonstrate that SK9 containing peptides readily form classic amyloid structures consistent with predictions of amyloid aggregation algorithms. In vivo, overexpression of proteases such as neutrophil elastase during inflammation can potentially lead to C-terminal peptides containing SK9. We also demonstrate that SK9 can promote the fibrillization of SAA, a protein marker of acute inflammation.

Our investigations reveal that the aromatic residues Phe2 and Tyr3 of SK9 play a pivotal role in its amyloidogenic function. We show that the primary sites of SK9-SAA binding lie in the amyloidogenic hotspots of SAA itself. Our results highlight two possible complications of SARS CoV-2 infection in individuals with hyper-inflammation either due to amyloids arising from SK9 containing peptides or SK9-induced AA amyloidosis.

Source: Asal Nady, Sean E. Reichheld, Simon Sharpe. An amyloidogenic fragment of the SARS CoV-2 envelope protein promotes serum amyloid A misfolding and fibrillization. bioRxiv 2024.04.25.591137; doi: https://doi.org/10.1101/2024.04.25.591137 https://www.biorxiv.org/content/10.1101/2024.04.25.591137v1.full (Full text)

Dermatologic Changes in Experimental Model of Long-COVID

Abstract:

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits.
In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored.
For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans.
In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers.
Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.
Source: Hussain, H.; Paidas, M.J.; Rajalakshmi, R.; Fadel, A.; Ali, M.; Chen, P.; Jayakumar, A.R. Dermatologic Changes in Experimental Model of Long-COVID. Preprints 2023, 2023122339. https://doi.org/10.20944/preprints202312.2339.v1 https://www.preprints.org/manuscript/202312.2339/v1 (Full text available as PDF file)

Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2—New Data for a Possible Role in the Long COVID Pattern

Abstract:

It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations.
In other autoimmune diseases, such as Parkinson’s disease (PD) or Alzheimer’s Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling.  After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment.
It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.
Source: Brogna C, Cristoni S, Brogna B, Bisaccia DR, Marino G, Viduto V, Montano L, Piscopo M. Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2—New Data for a Possible Role in the Long COVID Pattern. Biomedicines. 2023; 11(1):87. https://doi.org/10.3390/biomedicines11010087 https://www.mdpi.com/2227-9059/11/1/87 (Full text)

Asthenic disorders as a manifestation of chronic fatigue syndrome

Abstract:

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.

Source: Putilina MV. Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti [Asthenic disorders as a manifestation of chronic fatigue syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(8):125-130. Russian. doi: 10.17116/jnevro2021121081125. PMID: 34481448. [Abstract in English, Russian] https://pubmed.ncbi.nlm.nih.gov/34481448/

A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and chronic fatigue syndrome

Abstract:

Background: Q fever fatigue syndrome (QFS) is a well-documented state of prolonged fatigue following around 20% of acute Q fever infections. It has been hypothesized that low grade inflammation plays a role in its aetiology. In this study, we aimed to identify transcriptome profiles that could aid to better understand the pathophysiology of QFS.

Methods: RNA of monocytes was collected from QFS patients (n = 10), chronic fatigue syndrome patients (CFS, n = 10), Q fever seropositive controls (n = 10), and healthy controls (n = 10) who were age- (± 5 years) and sex-matched. Transcriptome analysis was performed using RNA sequencing.

Results: Mitochondrial-derived peptide (MDP)-coding genes MT-RNR2 (humanin) and MT-RNR1 (MOTS-c) were differentially expressed when comparing QFS (− 4.8 log2-fold-change P = 2.19 × 10−9 and − 4.9 log2-fold-change P = 4.69 × 10−8), CFS (− 5.2 log2-fold-change, P = 3.49 × 10−11 − 4.4 log2-fold-change, P = 2.71 × 10−9), and Q fever seropositive control (− 3.7 log2-fold-change P = 1.78 × 10−6 and − 3.2 log2-fold-change P = 1.12 × 10−5) groups with healthy controls, resulting in a decreased median production of humanin in QFS patients (371 pg/mL; Interquartile range, IQR, 325–384), CFS patients (364 pg/mL; IQR 316–387), and asymptomatic Q fever seropositive controls (354 pg/mL; 292–393).

Conclusions: Expression of MDP-coding genes MT-RNR1 (MOTS-c) and MT-RNR2 (humanin) is decreased in CFS, QFS, and, to a lesser extent, in Q fever seropositive controls, resulting in a decreased production of humanin. These novel peptides might indeed be important in the pathophysiology of both QFS and CFS.

Source: Ruud P. H. Raijmakers, Anne F. M. Jansen, Stephan P. Keijmel, Rob ter Horst, Megan E. Roerink, Boris Novakovic, Leo A. B. Joosten, Jos W. M. van der Meer, Mihai G. Netea and Chantal P. Bleeker-Rovers. A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and chronic fatigue syndrome. Journal of Translational Medicine 2019 17:157  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1906-3  (Full article)

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis.

We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature.

By combining results from unsupervised and supervised analyses, a candidate immunosignature with 654 peptides was able to differentiate ME/CFS from controls. The immunosignature was tested and further refined using the Norwegian and USA samples. This resulted in a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls in the international data sets.

We were able to identify a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation. By extending testing of both our signature and one previously reported in the literature to larger cohorts, and further interrogating the specific peptides we and others have identified, we may deepen our understanding of the origins of ME/CFS and work towards a clinically meaningful diagnostic biomarker.

Source: Günther, O.P., Gardy, J.L., Stafford, P. et al. Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Mol Neurobiol (2018). https://doi.org/10.1007/s12035-018-1354-8  https://link.springer.com/article/10.1007%2Fs12035-018-1354-8 (Full article)