The state of complement in COVID-19

Nature reviews. Immunology, Год журнала: 2021, Номер 22(2), С. 77 - 84

Опубликована: Дек. 15, 2021

Язык: Английский

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Therapeutic Targeting of NF-κB in Acute Lung Injury: A Double-Edged Sword

Cells, Год журнала: 2022, Номер 11(20), С. 3317 - 3317

Опубликована: Окт. 21, 2022

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating disease that can be caused by variety of conditions including pneumonia, sepsis, trauma, and most recently, COVID-19. Although our understanding the mechanisms ALI/ARDS pathogenesis resolution has considerably increased in recent years, mortality rate remains unacceptably high (~40%), primarily due to lack effective therapies for ALI/ARDS. Dysregulated inflammation, as characterized massive infiltration polymorphonuclear leukocytes (PMNs) into airspace associated damage capillary-alveolar barrier leading pulmonary edema hypoxemia, major hallmark Endothelial cells (ECs), inner lining blood vessels, are important cellular orchestrators PMN lung. Nuclear factor-kappa B (NF-κB) plays an essential role rendering endothelium permissive adhesion transmigration reach inflammatory site. Thus, targeting NF-κB provides attractive approach mitigate PMN-mediated vascular injury, not only ALI/ARDS, but other diseases well which EC dysfunction pathogenic mechanism. This review discusses regulation context inflammation evaluates potential problems it therapy

Язык: Английский

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Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Cells, Год журнала: 2023, Номер 12(5), С. 688 - 688

Опубликована: Фев. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Язык: Английский

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SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 15, 2024

Abstract Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element human tissues reservoirs is the main product of mRNA COVID-19 vaccines. We investigated whether alone triggers pro-inflammatory pro-coagulant responses primary cultures two cell types deeply affected by SARS-CoV-2, such monocytes cells. Methods In umbilical vein cells (HUVEC) monocytes, components NF-κB NLRP3 inflammasome system, well coagulation regulators, were assessed qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results activated NF-κB, promoted cytokines release, triggered priming activation system resulting mature IL-1β formation both types. This was paralleled enhanced production factors von Willebrand factor (vWF), VIII tissue factor, that mediated, at least part, IL-1β. Additionally, failed to enhance ADAMTS-13 levels counteract activity vWF multimers. Monocytes HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches gene silencing showed TLR4 receptors mediated effects but not HUVEC. Conclusion behaves a stimulus Interfering with signaling pathways evoked may help preventing immune vascular complications driven viral element.

Язык: Английский

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Complement activation in COVID-19 and targeted therapeutic options: A scoping review

Blood Reviews, Год журнала: 2022, Номер 57, С. 100995 - 100995

Опубликована: Июль 31, 2022

Increasing evidence suggests that activation of the complement system plays a key role in pathogenesis and disease severity Coronavirus 2019 (COVID-19). We used systematic approach to create an overview COVID-19 based on histopathological, preclinical, multiomics, observational clinical interventional studies. A total 1801 articles from PubMed, EMBASE Cochrane was screened which 157 were included this scoping review. Histopathological, multiomics studies showed apparent through all three pathways correlation with mortality. The targeted at different levels COVID-19, C5 C5a inhibition seem most promising. Adequately powered, double blind RCTs are necessary order further investigate effect targeting COVID-19.

Язык: Английский

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SARS-CoV-2 and the spike protein in endotheliopathy

Trends in Microbiology, Год журнала: 2023, Номер 32(1), С. 53 - 67

Опубликована: Июнь 12, 2023

Язык: Английский

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Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

Biomedicines, Год журнала: 2023, Номер 11(2), С. 451 - 451

Опубликована: Фев. 3, 2023

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses Spike proteins of its envelope infecting target cells expressing on membrane angiotensin converting enzyme 2 (ACE2) that acts as a receptor. To control pandemic, genetically engineered vaccines have been designed inducing neutralizing antibodies against proteins. These do not act like traditional protein-based vaccines, they deliver message in form mRNA or DNA to host then produce and expose protein (from which it can be shed soluble form) alert immune system. Mass vaccination has brought light various adverse effects associated with these based mainly affecting circulatory cardiovascular ACE2 is present membrane-bound several cell types, including mucosa upper gastrointestinal tracts, endothelium, platelets, plasma. converts vasoconstrictor II into peptides vasodilator properties. Here we review pathways immunization molecular mechanisms through protein, either from encoded by mRNA-based interferes Renin-Angiotensin-System governed ACE2, thus altering homeostasis circulation Understanding interactions consequent impact system will direct diagnosis therapy vaccine-related provide information development personalized considers pathophysiological conditions predisposing such events.

Язык: Английский

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Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know

Immunobiology, Год журнала: 2023, Номер 228(3), С. 152393 - 152393

Опубликована: Май 1, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was identified in China 2019 as the causative agent of COVID-19, and quickly spread throughout world, causing over 7 million deaths, which occurred prior to introduction first vaccine. In following discussion, while recognising that complement is just one many players we focus on relationship between COVID-19 disease, with limited digression into directly-related areas such complement, kinin release, coagulation. Prior outbreak, an important role for diseases had been established. Subsequently, multiple investigations patients confirmed dysregulation likely be a major driver disease pathology, some, if not all, patients. These data fuelled evaluation complement-directed therapeutic agents small patient cohorts, claims significant beneficial effect. As yet, these early results have reflected larger clinical trials, posing questions who treat, appropriate time duration treatment, optimal target treatment. While control pandemic has achieved through global scientific medical effort comprehend etiology extensive SARS-CoV-2 testing quarantine measures, vaccine development, improved therapy, possibly aided by attenuation dominant strains, it yet over. this review, summarise complement-relevant literature, emphasise its main conclusions, formulate hypothesis involvement COVID-19. Based make suggestions how any future outbreak might better managed order minimise impact

Язык: Английский

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Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement

Annals of Hematology, Год журнала: 2023, Номер 102(6), С. 1307 - 1322

Опубликована: Апрель 19, 2023

Язык: Английский

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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(24), С. 15480 - 15480

Опубликована: Дек. 7, 2022

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein glycoconjugates on surfaces red blood cells (RBCs), other and endothelial are key infectivity morbidity COVID-19. To provide further insight into these their potential clinical relevance, classic hemagglutination (HA) assay was applied using Wuhan, Alpha, Delta Omicron B.1.1.529 lineages mixed with human RBCs. The electrostatic central region four studied through molecular modeling simulations. Inhibition protein-induced HA tested macrocyclic lactone ivermectin (IVM), which is indicated bind strongly sites. results experiments were, first, induced HA. at a significantly lower threshold concentration than three prior much more electropositive its region. IVM blocked when added RBCs reversed afterward. These validate extend role bindings viral in They furthermore suggest therapeutic options competitive glycan-binding agents such as may help elucidate rare serious adverse effects (AEs) associated COVID-19 mRNA vaccines, use generated antigen.

Язык: Английский

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