Immunoinformatic approach to design T cell epitope-based chimeric vaccine targeting multiple serotypes of dengue virus DOI
Nilanshu Manocha, Prakash Jha, Prashant Kumar

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Nov. 28, 2024

The global dengue outbreak is a significant public health concern, with the World Health Organization recording over 3 million cases and 0.04% case fatality rate until July 2023. infection anticipated to rise in vulnerable regions worldwide. While live-attenuated vaccines are current standard, their effectiveness certain populations debated. Furthermore, presence of four closely related virus serotypes can lead antibody-dependent enhancement, compromising vaccine efficacy. In response, we propose development therapeutic subunit-vaccine based on epitopes from all induce robust cross-protective cellular immunity. Our approach involves designing multi-epitope chimeric immunogen using envelope protein virus. MHC-I MHC-II binding T-cell were selected antigen processing criteria. most potent immunodominant for each serotype, considering immunogenicity, population coverage, prediction scores, combined AAY linker peptides create stable polypeptide. Predicted be both antigenic non-allergenic, design exhibits soluble tertiary structure half-life 4.4 h mammalian systems. addition, employed an agonist toll-like receptor-4 at N-terminal downstream immunostimulatory validated through docking molecular dynamics simulations. This construct shows promise eliciting effective immune response against serotypes.

Language: Английский

Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology DOI Creative Commons
Matthew Halma, Paul E. Marik,

Yusuf M. Saleeby

et al.

Endocrine and Metabolic Science, Journal Year: 2024, Volume and Issue: 14, P. 100163 - 100163

Published: Jan. 30, 2024

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest the field of medicine. In this article, we delve into mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore potential fasting on protein-related pathology role interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, metformin. conclusion, fasting, coupled an understanding nuances, holds promise as intervention SARS-CoV-2 related diseases; broad implications human health. This review presents possibility using treat diseases, details deploy modality.

Language: Английский

Citations

3
Cellular signalling by SARS-CoV-2 spike protein DOI Creative Commons
Nicholas P. Gracie, Lachlan Yuek Shun Lai, Timothy P. Newsome

et al.

Microbiology Australia, Journal Year: 2024, Volume and Issue: 45(1), P. 13 - 17

Published: March 22, 2024

Following the release of SARS-CoV-2 genome, spike protein was identified as key viral mediating cell entry. In addition to its critical function in delivering genome host cytoplasm, is able activate diverse signalling pathways, leading notable cellular responses, including inflammation, remodelling, and immune evasion. The associated with induction a ‘cytokine storm’ characterised by elevated levels proinflammatory cytokines like IL-6 IL-1β. Moreover, deregulates TGF-β E-selectin, fibrotic injury tissue scarring notably pulmonary tissues. Finally, plays role evasion, disrupting Type I interferon responses. Understanding these interactions effects crucial for comprehending pathogenesis COVID-19 developing effective therapeutic strategies.

Language: Английский

Citations

3
Near-Infrared Light Exposure Triggers ROS to Downregulate Inflammatory Cytokines Induced by SARS-CoV-2 Spike Protein in Human Cell Culture DOI Creative Commons
Blanche Aguida,

Marie-Marthe Chabi,

Soria Baouz

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(10), P. 1824 - 1824

Published: Oct. 2, 2023

The leading cause of mortality from SARS-CoV-2 is an exaggerated host immune response, triggering cytokine storms, multiple organ failure and death. Current drug- vaccine-based therapies are limited efficacy against novel viral variants. Infrared therapy a non-invasive safe method that has proven effective inflammatory conditions for over 100 years. However, its mechanism action poorly understood not received widespread acceptance. We herein investigate whether near-infrared (NIR) light exposure in human primary alveolar macrophage cells could downregulate cytokines triggered by the spike (S) protein or lipopolysaccharide (LPS), via what underlying mechanism. Our results showed dramatic reduction pro-inflammatory within days NIR treatment, while anti-inflammatory were upregulated. Mechanistically, stimulated mitochondrial metabolism, induced transient bursts reactive oxygen species (ROS) activated antioxidant gene transcription. These, turn, downregulated ROS cytokines. A causal relationship was shown between induction cellular downregulation S. If confirmed clinical trials, this would provide immediate defense variants other infectious diseases.

Language: Английский

Citations

7
Neuroprotective effect of emodin on Aβ25-35-induced cytotoxicity in PC12 cells involves Nrf2/GPX4 and TLR4/p-NF-κB/NLRP3 pathways DOI

Nengyin Xia,

Lingyun Xu,

Dengrui Xu

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1841, P. 149019 - 149019

Published: May 23, 2024

Language: Английский

Citations

2
Humoral Innate Immunity and Acute-Phase Proteins DOI
Alberto Mantovani, Cecília Garlanda

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(18), P. 1725 - 1726

Published: May 3, 2023

Language: Английский

Citations

4
Design of a novel multi-epitope vaccine candidate against Chlamydia trachomatis using structural and nonstructural proteins: an immunoinformatics study DOI
Hussein T. Abdulabbas,

Alaa Naseer Mohammad Ali,

Akbar Farjadfar

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(8), P. 4356 - 4369

Published: June 8, 2023

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium which causes eye and sexually transmitted infections. During pregnancy, the associated with preterm complications, low weight of neonates, fetal demise endometritis leading to infertility. The aim our study was design a multi-epitope vaccine (MEV) candidate against C. trachomatis. After protein sequence adoption from NCBI, potential epitopes toxicity, antigenicity, allergenicity, MHC-I MHC-II binding, cytotoxic T lymphocytes (CTLs), Helper (HTLs) interferon-γ (IFN-γ)- induction were predicted. adopted fused together using appropriate linkers. In next step, MEV structural mapping characterization, three-dimensional (3D) structure homology modeling refinement also performed. interaction toll-like receptor 4 (TLR4) docked. immune responses simulation assessed C-IMMSIM server. Molecular dynamic (MD) verified stability TLR4-MEV complex. Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach demonstrated high affinity binding TLR4, MHC-II. construct stable water soluble had enough antigenicity lacked allergenicity stimulation cells B INF-γ release. confirmed acceptable both humoral cellular arms. It proposed that in vitro vivo studies are needed evaluate findings this study.Communicated by Ramaswamy H. Sarma

Language: Английский

Citations

4
TLR4 sensitizes plasmacytoid dendritic cells for antiviral response against SARS-CoV-2 coronavirus DOI Open Access
King Hoo Lim, Lishi Wang, Eunice Dotse

et al.

Journal of Leukocyte Biology, Journal Year: 2023, Volume and Issue: 115(1), P. 190 - 200

Published: Sept. 25, 2023

Abstract Plasmacytoid dendritic cells are a rare subset of that exhibit antiviral functions in response to toll-like receptor 7/8 stimulations. Alternative receptors such as TLR4 have been known be active plasmacytoid for immune regulatory functions. However, it is unclear whether these differentially activate compared with canonical stimulation. Here, we assessed alternative cell activation states mediated by other than endosomal via the RNA sequencing approach. We found 4 stimulation induced high degree similarity gene expression pattern cells. Despite resemblance 7/8, discovered unique genes were activated under only, well at higher magnitude comparison activation. In between 4–activated and conventional cells, revealed expressed distinct sets, whereby mostly favored antigen presentation adaptive regulation while leaned toward against infectious diseases. Last, determined sensitized SARS-CoV-2 (COVID-19) single-stranded enhancing antiviral-related responses type I interferon production. These findings provided greater insights into state which can beneficial therapeutic interventions involving various

Language: Английский

Citations

4
Impacts of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review DOI Open Access

Annelise Bocquet-Garçon

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: March 26, 2024

The Spike protein enables the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to multiple receptors, including angiotensin-converting enzyme (ACE2). Scientific studies also indicate that is involved in forms of disease 2019 (COVID-19), "long-haul COVID diseases" - known as "long syndromes" or "post-acute sequelae SARS-CoV-2 infection" (PACS) or, recently, adverse reactions lipid nanoparticle-messenger ribonucleic acid (mRNA) vaccines other anti-COVID19 products. Numerous mutations, notably within subunit 1 (S1), prevent neutralization antibodies, but more generally, virus has developed numerous strategies avoid immune system surveillance, especially type-I interferons (IFN-I). Meanwhile, a "hyperinflammatory" state, named "cytokine storm," sets in. However, what role does play escape mechanisms? Can its inflammatory activities affect IFN-I? Does block IFN-I hijack them for benefits? What are potential consequences? This article was written provide an up-to-date and general overview impact on innate effectors at molecular level.

Language: Английский

Citations

1
FSTL1 and TLR4 interact with PEDV structural proteins to promote virus adsorption to host cells DOI Creative Commons

Chunyun Liu,

Ning Kong, Hailong Liu

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 99(1)

Published: Dec. 13, 2024

Infection with porcine epidemic diarrhea virus (PEDV) results in enormous economic damage to the global swine industry. PEDV starts its life cycle by binding receptors of host cells and adsorbing onto cellular surfaces. However, it is still unknown how adsorbs surface mechanism beneath interplay cell transmembrane protein proteins. FSTL1, which a secreted glycoprotein, participates diverse pathological physiological processes, including immune modulation proliferation differentiation. The protein, TLR4, serves as pattern recognition receptor recognizing broad spectrum pathogens, exerts crucial effect on system. In this study, we identified that FSTL1 promoted infection. Further studies demonstrated interactive relationship between structural proteins (N S2). addition, also confirmed TLR4 interacted N, S1, S2 surface. Moreover, interaction induced viral adsorption cells. This study offers explicit evidence act mediators for interacting N/S proteins.IMPORTANCEAs highly infectious (PEDV)-induced intestinal condition swine, (PED) 100% death rate among suckling piglets poses serious burden farming. Therefore, essential investigate infection, replication, proliferation. Virus begins remains unclear revealed N proteins, while (N, thoroughly methodically was engaged internalization attachment processes promoting N\S

Language: Английский

Citations

1
Sensitive detection of lipopolysaccharides by monitoring of interleukin-10 secretion from human PBMCs. DOI
Daniel Ivanusic, Joachim Denner

PubMed, Journal Year: 2023, Volume and Issue: 2023

Published: Jan. 1, 2023

Lipopolysaccharide (LPS) contaminations may falsify immunological experiments and are crucial for pharmaceutical products because they cause life-threatening immune reactions. Here, we present interleukin-10 (IL-10) as a reliable marker to measure LPS contents when the readout of pro-inflammatory cytokines is not favored. This animal free source assay able detect with limit detection (LOD) 0.024 EU/ml by monitoring IL-10 secretions from isolated human peripheral blood mononuclear cells (PBMCs).

Language: Английский

Citations

2