Synthetic peptide TEKKRRETVEREKE derived from ezrin induces differentiation of NIH/3T3 fibroblasts

Chulkina, Marina; Negmadjanov, Ulugbek; Лебедева, Екатерина; Пичугин, А.В.; Mazurov, Dmitriy; Ataullakhanov, Ravshan; Holmuhamedov, Ekhson

doi:10.1016/j.ejphar.2017.06.033

Cited by 4 publications

(3 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Higher IgG antibody titres have also been observed with Human Ezrin Peptide treatment in combination with hepatitis B vaccination. Human Ezrin Peptides may bind the "Receptor" conformation of ezrin to trigger the formation and activation of the multi-protein-complex of CFTR+NHERF+NHE+ezrin+PKC+PKA [54][55][56].…”

Section: Discussionmentioning

confidence: 99%

The COVID-19 Cell Signalling Problem: Spike, RAGE, PKC, p38, NFκB & IL-6 Hyper-Expression and the Human Ezrin Peptide, VIP, PKA-CREB Solution

Holms¹

2022

Immuno

View full text Add to dashboard Cite

SARS-CoV-2 infection inhibits interferon expression, while hyper-activating innate-immune signalling and expression of pro-inflammatory cytokines. SARS-CoV-2 proteins: Spike, M and nsp6, nsp12 and nsp13 inhibit IFR3-mediated Type-1-interferon defence, but hyper-activate intracellular signalling, which leads to dysfunctional expression of pro-inflammatory cytokines, particularly IL-1β IL-6, IL-8, and TNFα. Ezrin, a sub-membrane adaptor-protein, organises multi-protein-complexes such as ezrin+NHERF1+NHE+CFTR, which control the density and location of ACE2 receptor expression on the luminal surface of airway-epithelial-cells, as well as determining susceptibility to SARS-CoV-2 infection. This protein complex is vital for lung-surfactant production for efficient gas-exchange. Ezrin also forms multi-protein-complexes that regulate signalling kinases; Ras, PKC, PI3K, and PKA. m-RAGE is a pattern-recognition-receptor of the innate immune system that is triggered by AGEs, which are chemically modified proteins common in the elderly and obese. m-RAGE forms multi-protein complexes with ezrin and TIRAP, a toll-like-receptor adaptor-protein. The main cause of COVID-19 is not viral infection but pro-inflammatory p38MAPK signalling mediated by TLRs and RAGE. In contrast, it appears that activated ezrin+PKA signalling results in the activation of transcription-factor CREB, which suppresses NFκB mediated pro-inflammatory cytokine expression. In addition, competition between ezrin and TIRAP to form multi-protein-complexes on membrane PIP2-lipid-rafts is a macromolecular-switch that changes the priority from innate immune activation programs to adaptive immune activation programs. Human Vasoactive Intestinal Peptide (VIP), and Human Ezrin Peptides (HEP-1 and RepG3) probably inhibit COVID-19 by activating the ezrin+PKA and ras>Raf>MEK>ERK>RSK>CREB>IL-10 signalling, which favours activation of adaptive immunity programs and inhibition of the dysfunctional innate-inflammation, the cause of COVID-19. HEP-1, RepG3, and VIP in individual human volunteers and in small clinical studies have been shown to be effective COVID-19 therapies, and seem to have a closely related mechanism of action.

show abstract

Section: Discussionmentioning

confidence: 99%

The COVID-19 Cell Signalling Problem: Spike, RAGE, PKC, p38, NFκB & IL-6 Hyper-Expression and the Human Ezrin Peptide, VIP, PKA-CREB Solution

Holms¹

2022

Immuno

View full text Add to dashboard Cite

show abstract

“…It was shown that the human ezrin peptide 324-337, HEP1 (TEKKRRETVEREKE), was very effective in the treatment of hepatitis C virus (HCV), accelerated and facilitated wound and ulcer healing in clinical applications, and was well tolerated [46,47]. This peptide was used in a randomised, double-blind phase I study to investigate the efficacy and safety of the peptides in COVID-19 patients [48].…”

Section: Antiviral Activitymentioning

confidence: 99%

Peptides in COVID-19 Clinical Trials—A Snapshot

Hilpert

2021

Biologics

View full text Add to dashboard Cite

Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview.

show abstract

“…Following engagement of the B-cell receptor (BCR) with antigen, B-cells contribute to the adaptive immune response to viral infection by transforming into antibody-producing plasma cells and long-lived memory cells. Ezrin is directly involved in cellular responsiveness and transmembrane signalling in B cells [ 52 ]. Ezrin and actin forms a protein complex with the BCR and coordinates the early events of B-cell activation to antigens [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

Ezrin Peptide Therapy from HIV to COVID: Inhibition of Inflammation and Amplification of Adaptive Anti-Viral Immunity

Holms¹,

Ataullakhanov

2021

IJMS

View full text Add to dashboard Cite

Human Ezrin Peptides (HEPs) are inhibitors of expression of IL-6 and other inflammatory cytokines, amplifiers of adaptive B cell and T cell immunity and enhancers of tissue repair. The mutation stable C-terminus of HIV gp120, mimics 69% of the “Hep-receptor”, a zipped α-helical structure in the middle of the α domain of human ezrin protein. Synthetic peptides homologous to the Hep-receptor of ezrin of five to fourteen amino acids, activate anti-viral immunity against a wide range of viruses (HIV, HCV, herpes, HPV, influenza and other human respiratory viruses). Human Ezrin Peptide One (HEP1) TEKKRRETVEREKE (brand name Gepon, registered for human use in Russia from 2001) is a successful treatment for opportunistic infections in HIV-infected patients. That treats HEP1and prevents mucosal candidiasis, herpes zoster outbreaks and infection-induced chronic diarrhea. There are clinical publications in Russian on the successful treatments of chronic recurrent vaginal candidiasis, acute and chronic enterocolitis and dysbacteriosis, which are accompanied by normalization of the mucosal microbiome, and the decline or disappearance of inflammation. HEP1 is also an effective treatment and prevention for recurrent inflammation and ulceration in the stomach, duodenum and colon. HEP1 and RepG3 GEKKRRETVEREGG (a derivative of HEP1) have been used successfully as an inhaled spray peptide solution to treat a small number of human volunteers with mild-to-moderate COVID, resulting from SARS-CoV-2 infection, based on earlier successes in treating acute viral respiratory disease with inflammatory complications. Ezrin peptides seem to correct a dysregulation of innate immune responses to SARS-CoV-2. They are also adjuvants of B cell adaptive immunity and increase antibody titres, resulting in protection from lethal virus infection of mice. In a clinical study in Moscow, orally administered HEP1 was shown to enhance antibody-titres produced in response to hepatitis-B vaccination. These very preliminary but promising results with ezrin peptide treatment of COVID must be replicated in large-scale randomised placebo controlled clinical studies, to be verified.

show abstract

Synthetic peptide TEKKRRETVEREKE derived from ezrin induces differentiation of NIH/3T3 fibroblasts

Cited by 4 publications

References 73 publications

The COVID-19 Cell Signalling Problem: Spike, RAGE, PKC, p38, NFκB & IL-6 Hyper-Expression and the Human Ezrin Peptide, VIP, PKA-CREB Solution

The COVID-19 Cell Signalling Problem: Spike, RAGE, PKC, p38, NFκB & IL-6 Hyper-Expression and the Human Ezrin Peptide, VIP, PKA-CREB Solution

Peptides in COVID-19 Clinical Trials—A Snapshot

Ezrin Peptide Therapy from HIV to COVID: Inhibition of Inflammation and Amplification of Adaptive Anti-Viral Immunity

Contact Info

Product

Resources

About