Variant-Specific Interactions at the Plasma Membrane: Heparan Sulfate’s Impact on SARS-CoV-2 Binding Kinetics DOI Creative Commons
Dario Valter Conca, Fouzia Bano, Małgorzata Graul

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

The spread of SARS-CoV-2 led to the emergence several variants concern (VOCs). spike glycoprotein, responsible for engaging viral receptor, exhibits highest density mutations, suggesting an ongoing evolution optimize entry. This study characterizes bond formed by virion mimics carrying protein and plasma membrane host cells in early stages virus Contrary traditional analysis isolated ligand–receptor pairs, we utilized well-defined biomimetic models biochemical biophysical techniques characterize multivalent interaction VOCs with complex cell membrane. We observed overall increase binding affinity newer VOCs. By progressively reducing system complexity, identify heparan sulfate (HS) as a main driver this variation, 10-fold Omicron BA.1 over that original strain. These results demonstrate essential role coreceptors, particularly HS, modulation infection highlight importance multiscale assays account complexity fully understand molecular components their synergy attachment

Language: Английский

Mucosal immune response in biology, disease prevention and treatment DOI Creative Commons
Xiaoxue Zhou, Yuchen Wu,

Zhipeng Zhu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Language: Английский

Citations

4
Spike-heparan sulfate interactions in SARS-CoV-2 infection DOI Creative Commons
Fiona L. Kearns, Daniel R. Sandoval, Lorenzo Casalino

et al.

Current Opinion in Structural Biology, Journal Year: 2022, Volume and Issue: 76, P. 102439 - 102439

Published: July 6, 2022

Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection SARS-CoV-2 by facilitating so-called open conformation spike protein, which is required for binding to ACE2. This review highlights involvement sulfate cycle argues there high degree coordination between host cell asparagine-linked glycans on enabling ACE2 subsequent infection. The discovery protein depends both viral provides insights into evolution, spread potential therapies its variants.

Language: Английский

Citations

69
Infection and transmission of SARS‐CoV‐2 depend on heparan sulfate proteoglycans DOI Creative Commons
Marta Bermejo‐Jambrina, Julia Eder,

Tanja M. Kaptein

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(20)

Published: Sept. 12, 2021

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with binding to proteoglycans, which might be an additional mechanism neutralize infection. infection epithelial cells was blocked low molecular weight heparins (LMWH). Although dendritic (DCs) mucosal Langerhans (LCs) were not infected SARS-CoV-2, both DC subsets efficiently captured via transmitted virus ACE2-positive cells. human primary nasal pre-treatment LMWH. These data strongly suggest that are important facilitating transmission, support use LMWH prophylaxis

Language: Английский

Citations

68
The role of dendritic cells in COVID-19 infection DOI Creative Commons
Xuying Wang, Fei Guan,

H. I. Miller

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)

Published: March 22, 2023

The persistent pandemic of coronavirus disease in 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) currently poses a major infectious threat to public health around the world. COVID-19 is an characterized strong induction inflammatory cytokines, progressive lung inflammation, and potential multiple organs dysfunction. SARS-CoV-2 infection closely related innate immune system adaptive system. Dendritic cells (DCs), as "bridge" connecting immunity immunity, play many important roles viral diseases. In this review, we will pay special attention possible mechanism dendritic human transmission clinical progression diseases, well reduction dysfunction DCs infection, so understand immunological characteristics infection.

Language: Английский

Citations

25
Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium DOI Creative Commons
Anaëlle Muggeo, Christelle Coraux, Thomas Guillard

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(3), P. e1011221 - e1011221

Published: March 30, 2023

Pseudomonas aeruginosa is a major, but opportunistic, respiratory pathogen, which rarely infects healthy individuals, mainly due to the barrier effect of human airway epithelium (HAE). This review explores interaction P. with HAE and progression infection. The basolateral part epithelium, includes membrane epithelial cells basement membrane, inaccessible in normal tight epithelia intact junctions. We highlight how exploits weaknesses gain access epithelium. crucial initiate infection observed injured repairing or chronically remodeled during extrusion senescent cell multiplication renewal. subsequent adhesion bacteria cytotoxic action virulence factors, including toxins delivered by type 3 secretion system (T3SS), lead retractions death. Eventually, progressively reaches propagates radially through basal disseminate using twitching flagellar motility.

Language: Английский

Citations

24
Coreceptor functions of cell surface heparan sulfate proteoglycans DOI
Kazutaka Hayashida, Rafael Santos de Aquino, Pyong Woo Park

et al.

AJP Cell Physiology, Journal Year: 2022, Volume and Issue: 322(5), P. C896 - C912

Published: March 23, 2022

Receptor-ligand interactions play an important role in many biological processes by triggering specific cellular responses. These are frequently regulated coreceptors that facilitate, alter, or inhibit signaling. Coreceptors work parallel with other and accessory molecules to coordinate receptor-ligand interactions. Cell surface heparan sulfate proteoglycans (HSPGs) function as unique because they can bind ligands receptors through their HS core protein motifs. HSPGs typically expressed abundance of the signaling and, thus, capable mediating initial binding cell surface. HSPG do not possess kinase domains intrinsic enzyme activities for most part, does directly stimulate intracellular Because these features, primarily Given widely conserved, likely serve fundamental functions preserve basic physiological processes. Indeed, support growth factors, morphogens, chemokines, extracellular matrix (ECM) components, microbial pathogens secreted virulence factors. Through interactions, regulate adhesion, proliferation, migration, differentiation, impact onset, progression, outcome pathophysiological processes, such development, tissue repair, inflammation, infection, tumorigenesis. This review seeks provide overview various mechanisms how coreceptors.

Language: Английский

Citations

32
Surface charge changes in spike RBD mutations of SARS-CoV-2 and its variant strains alter the virus evasiveness via HSPGs: A review and mechanistic hypothesis DOI Creative Commons

Zhongyun Zhang,

Juan Zhang, Jiqiu Wang

et al.

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 24, 2022

With the COVID-19 pandemic continuing, more contagious SARS-CoV-2 variants, including Omicron, have been emerging. The mutations, especially those that occurred on spike (S) protein receptor-binding domain (RBD), are of significant concern due to their potential capacity increase viral infectivity, virulence, and breakthrough antibodies' protection. However, molecular mechanism involved in pathophysiological change mutations remains poorly understood. Here, we summarized 21 RBD human angiotensin-converting enzyme 2 (hACE2) and/or neutralizing binding characteristics. We found most which could surface positive charge or polarity, enhanced hACE2 affinity immune evasion. Based dependence electrostatic interaction epitope residue virus docking (like receptors antibodies) for its invasion, postulated polarity changes novel S affect antibodies. Thus, modeled mutant trimers RBD-hACE2 complexes calculated electrotactic distribution study changes. Meanwhile, emphasized heparan sulfate proteoglycans (HSPGs) might play an important role hACE2-mediated entry into cells. Those hypotheses provide some hints how enhance fitness evasion, may indicate ways drug design, next-generation vaccine development, antibody therapies.

Language: Английский

Citations

31
Global impact of proteoglycan science on human diseases DOI Creative Commons
Christopher Xie, Liliana Schaefer, Renato V. Iozzo

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(11), P. 108095 - 108095

Published: Oct. 4, 2023

Language: Английский

Citations

17
Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans DOI
Yingcai Xiong,

Keyu Tao,

Li Tao

et al.

Food & Function, Journal Year: 2024, Volume and Issue: 15(4), P. 1948 - 1962

Published: Jan. 1, 2024

Resveratrol disrupts the early stages of RSV infection by engaging with HSPGs, thus impeding binding viral receptors. Resveratrol's affinity appears to be predominantly directed towards negatively charged sites on HSPGs.

Language: Английский

Citations

6
Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae DOI Creative Commons
N Panagiotides, Michael Poledniczek, Martin Andreas

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 121 - 121

Published: Jan. 14, 2024

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic removal disturbed during pathological processes leading to inflammation, but also hypoxia or due alterations vascular perfusion coagulability. degradation of the glycocalyx as main component endothelial barrier well pericyte disintegration results accumulation interstitial intracellular water. Moreover, dysfunction evokes an increase metabolic waste products, cytokines inflammatory cells space contributing oedema formation. This leads stiffness impaired contractility, eventually resulting cardiomyocyte apoptosis, remodelling fibrosis. following article reviews pathophysiological including myocarditis, ischaemia-reperfusion injury viral infections with special focus on pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications potential long-term effects persistence (long COVID), treatment options, are discussed.

Language: Английский

Citations

6